519 results match your criteria Amyloidosis Transthyretin-Related


Amyloid Cardiomyopathy in the Rare Transthyretin Tyr78Phe Mutation.

J Cardiovasc Transl Res 2019 Jan 2. Epub 2019 Jan 2.

Cardiovascular Unit, Department of Internal Medicine, University of Genova and San Martino Hospital, Viale Benedetto XV, 6, 16132, Genoa, Italy.

Tyr78Phe is a rare pathogenic transthyretin (TTR) mutation. Few previous reports described a late-onset hereditary transthyretin-related amyloidosis (ATTR-m) form with a variable phenotype, mainly dominated by neurological manifestations. We describe the case of a 69-year-old male with massive but asymptomatic cardiac infiltration and only subclinical neurological involvement, and review the literature to depict characteristics of the Tyr78Phe TTR mutation. Read More

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http://link.springer.com/10.1007/s12265-018-9859-0
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http://dx.doi.org/10.1007/s12265-018-9859-0DOI Listing
January 2019
2 Reads

A rare variant of transthyretin-related amyloidosis associated with exclusive cardiomyopathy in a Hong Kong Chinese patient.

J Cardiol Cases 2018 Dec 22;18(6):185-188. Epub 2018 Oct 22.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong, China.

Hereditary transthyretin-related amyloidosis (ATTR, MIM #105210), also previously known as familial amyloidotic polyneuropathy, is one of the most life-threatening types of amyloidosis. ATTR is inherited in autosomal dominant mode with variable penetrance. If untreated, it is a relentless and lethal disease. Read More

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http://dx.doi.org/10.1016/j.jccase.2018.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306574PMC
December 2018
1 Read

Recent Advances in Oligonucleotide-Based Therapy for Transthyretin Amyloidosis: Clinical Impact and Future Prospects.

Biol Pharm Bull 2018 ;41(12):1737-1744

Department of Pharmacy, Kumamoto University Hospital.

Transthyretin (TTR) amyloidosis, also known as transthyretin-related familial amyloidotic polyneuropathy (ATTR-FAP), is a fatal hereditary systemic amyloidosis caused by mutant forms of TTR. Although conventional treatments for ATTR-FAP, such as liver transplantation (LT) and TTR tetramer stabilizer, reportedly halt the progression of clinical manifestation, these therapies have several limitations. Oligonucleotide-based therapy, e. Read More

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http://dx.doi.org/10.1248/bpb.b18-00625DOI Listing
January 2018
1 Read

Quantitation of Tc-DPD uptake in patients with transthyretin-related cardiac amyloidosis.

Amyloid 2018 Sep;25(3):203-210

a National Amyloidosis Centre , UCL Medical School (Royal Free Campus) , London , UK.

Purpose: Transthyretin (ATTR) amyloidosis is a rare but serious infiltrative disease associated with a wide spectrum of morphologic and functional cardiac involvement. Tc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), initially developed as a bone-seeking radiotracer, is remarkably sensitive for imaging cardiac ATTR amyloid deposits. Our aim was to investigate the feasibility and utility of estimating Tc-DPD uptake in myocardial tissue; this has the potential to yield reliable quantitative information on cardiac amyloid burden, which is urgently required to monitor disease progression and response to novel treatments. Read More

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http://dx.doi.org/10.1080/13506129.2018.1520087DOI Listing
September 2018
1 Read

Oligonucleotide Drugs for Transthyretin Amyloidosis.

N Engl J Med 2018 11;379(21):2086

Johns Hopkins Medicine, Baltimore, MD

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http://www.nejm.org/doi/10.1056/NEJMc1810994
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http://dx.doi.org/10.1056/NEJMc1810994DOI Listing
November 2018
6 Reads

Oligonucleotide Drugs for Transthyretin Amyloidosis.

N Engl J Med 2018 11;379(21):2085-6

Hospital de Santo António, Porto, Portugal

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http://www.nejm.org/doi/10.1056/NEJMc1810994
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http://dx.doi.org/10.1056/NEJMc1810994DOI Listing
November 2018
6 Reads

The identification of a transthyretin variant p.D38G in a Chinese family with early-onset leptomeningeal amyloidosis.

J Neurol 2018 Nov 23. Epub 2018 Nov 23.

Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, 410013, People's Republic of China.

Familial amyloid polyneuropathies (FAPs) are life-threatening, autosomal dominant diseases resulting, in most instances, from transthyretin gene (TTR) variants. A small number of TTR variants lead to leptomeningeal amyloidosis (LA), which is a rare FAP subtype with late-onset central nervous system (CNS) impairment symptoms. Previous studies suggest that LA's CNS selectivity was due to complete endoplasmic reticulum-associated degradation of highly destabilized mutants in peripheral tissues. Read More

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http://dx.doi.org/10.1007/s00415-018-9125-zDOI Listing
November 2018
9 Reads

Oligonucleotide Drugs for Transthyretin Amyloidosis.

Authors:
Joel N Buxbaum

N Engl J Med 2018 Nov;379(21):2086

Scripps Research Institute, La Jolla, CA

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http://www.nejm.org/doi/10.1056/NEJMc1810994
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http://dx.doi.org/10.1056/NEJMc1810994DOI Listing
November 2018
5 Reads

Hereditary transthyretin-related amyloidosis.

Acta Neurol Scand 2019 Feb 23;139(2):92-105. Epub 2018 Oct 23.

Ludwig Boltzmann Institute for Experimental und Clinical Traumatology, Vienna, Austria.

Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder, predominantly manifesting as length-dependent, small fiber dominant, axonal polyneuropathy and frequently associated with cardiac disorders and other multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with the substitution Val30Met as the most frequent mutation. TTR mutations lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, and formation of amyloid fibrils, which are consecutively deposited extracellularly in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or the skin. Read More

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http://doi.wiley.com/10.1111/ane.13035
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http://dx.doi.org/10.1111/ane.13035DOI Listing
February 2019
12 Reads

Non-parametric estimation of survival in age-dependent genetic disease and application to the transthyretin-related hereditary amyloidosis.

PLoS One 2018 25;13(9):e0203860. Epub 2018 Sep 25.

Institute of Mathematics (INSMI), National Center for French Research (CNRS), Paris, France.

In genetic diseases with variable age of onset, survival function estimation for the mutation carriers as well as estimation of the modifying factors effects are essential to provide individual risk assessment, both for mutation carriers management and prevention strategies. In practice, this survival function is classically estimated from pedigrees data where most genotypes are unobserved. In this article, we present a unifying Expectation-Maximization (EM) framework combining probabilistic computations in Bayesian networks with standard statistical survival procedures in order to provide mutation carrier survival estimates. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203860PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155453PMC
September 2018
11 Reads

Insight into the specificity and severity of pathogenic mechanisms associated with missense mutations through experimental and structural perturbation analyses.

Hum Mol Genet 2019 Jan;28(1):1-15

Department of Physical Chemistry, University of Granada, Granada, Spain.

Most pathogenic missense mutations cause specific molecular phenotypes through protein destabilization. However, how protein destabilization is manifested as a given molecular phenotype is not well understood. We develop here a structural and energetic approach to describe mutational effects on specific traits such as function, regulation, stability, subcellular targeting or aggregation propensity. Read More

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http://dx.doi.org/10.1093/hmg/ddy323DOI Listing
January 2019
3 Reads

Evaluation of Syncope Reveals Cardiac Amyloidosis.

Kans J Med 2018 Aug 30;11(3):78-79. Epub 2018 Aug 30.

Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122881PMC
August 2018
2 Reads

[The Changing Appearance of Cardiac Amyloidosis].

Dtsch Med Wochenschr 2018 09 10;143(18):1335-1343. Epub 2018 Sep 10.

A fast and reliable diagnosis of cardiac amyloidosis requires a significant amount of clinical awareness. It is especially important to come to an early diagnosis in patients with cardiac AL amyloidosis in order to improve the otherwise unfavourable clinical course in these patients. There is a significant increase in the number of patients with cardiac amyloidosis of the ATTR wild-type variety. Read More

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http://dx.doi.org/10.1055/s-0043-109420DOI Listing
September 2018
1 Read
0.550 Impact Factor

Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy.

N Engl J Med 2018 Sep 27;379(11):1007-1016. Epub 2018 Aug 27.

From the Columbia University Vagelos College of Physicians and Surgeons (M.S.M.) and Pfizer (J.H.S., A.I.B., P.H., J.S., M.B.S.), New York; Syneos Health, Raleigh, NC (B.G.); University College London and St. Bartholomew's Hospital, London (P.M.E.); the Amyloidosis Center, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, and the University of Pavia, Pavia (G.M.), and the Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna (C.R.) - both in Italy; the Amyloidosis Center (CEPARM), Federal University of Rio de Janeiro, Rio de Janeiro (M.W-C.); the Amyloidosis Center, Medical University of Heidelberg, Heidelberg, Germany (A.V.K.); the Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (M.G.); Stanford University School of Medicine, Stanford, CA (R.W.); the French Referral Center for Cardiac Amyloidosis, Amyloidosis Mondor Network, GRC Amyloid Research Institute and Department of Cardiology, Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor, and INSERM Unité 955, Clinical Investigation Center 006, and DHU ATVB, Creteil, France (T.D.); Penn Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia (B.M.D.); the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); Cleveland Clinic, Cleveland (M.H.); the Medical University of South Carolina, Charleston (D.P.J.); and Pfizer, Groton, CT (T.A.P., S.R., M.S.).

Background: Transthyretin amyloid cardiomyopathy is caused by the deposition of transthyretin amyloid fibrils in the myocardium. The deposition occurs when wild-type or variant transthyretin becomes unstable and misfolds. Tafamidis binds to transthyretin, preventing tetramer dissociation and amyloidogenesis. Read More

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http://www.nejm.org/doi/10.1056/NEJMoa1805689
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http://dx.doi.org/10.1056/NEJMoa1805689DOI Listing
September 2018
14 Reads

Technetium-99m pyrophosphate cardiac SPECT in endomyocardial biopsy negative cardiac amyloidosis.

Radiol Case Rep 2018 Oct 19;13(5):925-928. Epub 2018 Jul 19.

Department of Radiology, Eastern Virginia Medical School, 600 Gresham Drive, Norfolk, VA 23507, USA.

Cardiac amyloidosis is an under-appreciated cause of heart failure. Establishing a diagnosis is important because traditional heart failure treatment regimens can worsen left ventricular failure in this disease. Endomyocardial biopsy is the gold standard for diagnosis; however, scintigraphy with radiolabeled phosphate derivatives and cardiac magnetic resonance imaging have been shown to have high sensitivity and specificity in diagnosing cardiac amyloidosis. Read More

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http://dx.doi.org/10.1016/j.radcr.2018.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073076PMC
October 2018
18 Reads

Progression of transthyretin (TTR) amyloidosis in donors and recipients after domino liver transplantation-a prospective single-center cohort study.

Transpl Int 2018 11 28;31(11):1207-1215. Epub 2018 Aug 28.

I. Department of Internal Medicine, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.

Liver transplantation (LT) is the first-line therapy in patients with transthyretin (TTR) amyloidosis and progressive familial amyloid polyneuropathy (FAP). Explanted organs from these patients can be used for domino liver transplantation (DLT). After DLT, de novo amyloidosis may develop in domino recipients (DR). Read More

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http://dx.doi.org/10.1111/tri.13326DOI Listing
November 2018
22 Reads

Phenotypic profile of Ile68Leu transthyretin amyloidosis: an underdiagnosed cause of heart failure.

Eur J Heart Fail 2018 Oct 2;20(10):1417-1425. Epub 2018 Aug 2.

Cardiology, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Italy.

Aims: Cardiac amyloidosis remains a great challenge for the cardiologist. One of the three main aetiological forms, transthyretin-related hereditary amyloidosis (ATTRm), can present with several phenotypes, depending mainly on the specific mutation. We aimed to characterize the phenotype of patients with ATTRm due to Ile68Leu mutation, comparing them to patients with wild-type transthyretin amyloidosis (ATTRwt). Read More

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http://dx.doi.org/10.1002/ejhf.1285DOI Listing
October 2018
10 Reads

Revisiting transthyretin related cardiac amyloidosis: Case report and review of literature.

Clin Pract 2018 Mar 16;8(2):1054. Epub 2018 May 16.

Department of Medicine-Division of Cardiology, Drexel University College of Medicine-Hahnemann University Hospital, Philadelphia, PA, USA.

Amyloidosis is a complex group of disorders that can involve many organs and cause their dysfunction. Cardiac involvement indicates worse prognosis and influences treatment strategies. Cardiac amyloidosis is an under-diagnosed entity and high index of clinical suspicion and careful interpretation of basic diagnostic tools such as electrocardiogram and echocardiography is needed for early detection. Read More

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http://dx.doi.org/10.4081/cp.2018.1054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047478PMC
March 2018
13 Reads

[What gnaws at the heart and gets on the nerves].

Authors:
Arnt V Kristen

Internist (Berl) 2018 Nov;59(11):1208-1213

Zentrum für Innere Medizin, Klinik für Kardiologie, Angiologie und Pneumologie, Universitätsklinik Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Deutschland.

Transthyretin is a transport protein for thyroxine and retinol-binding protein, which is mainly produced in the liver. Hereditary transthyretin-related amyloidosis (ATTR) is caused by one of more than 120 point mutations in the transthyretin gene and inherited as an autosomal dominant disorder. The mutations cause a reduction in the stability of the tetrameric structure and dissociation into dimers and monomers as the rate-limiting step in amyloid formation is promoted. Read More

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http://link.springer.com/10.1007/s00108-018-0470-x
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http://dx.doi.org/10.1007/s00108-018-0470-xDOI Listing
November 2018
10 Reads

Family dynamics in transthyretin-related familial amyloid polyneuropathy Val30Met: Does genetic risk affect family functioning?

Clin Genet 2018 Nov 14;94(5):401-408. Epub 2018 Aug 14.

Serviço de Psiquiatria e Saúde Mental, Centro Hospitalar do Porto, Porto, Portugal.

Adult-onset, chronic, genetic diseases like transthyretin-related familial amyloid polyneuropathy Val30Met (TTR-FAP Val30Met), have a major psychosocial impact not only on patients, but also on families. Genetic risk may therefore be an increased factor in psychosocial impact of the disease on these families' functioning. To evaluate impact of genetic risk, a study was conducted to perceive the impact of the illness on families' functioning. Read More

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http://dx.doi.org/10.1111/cge.13416DOI Listing
November 2018
15 Reads

Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis.

N Engl J Med 2018 Jul;379(1):22-31

From the Indiana University School of Medicine, Indianapolis (M.D.B.); Centro de Estudos em Paramiloidose Antônio Rodrigues de Mello, National Amyloidosis Referral Center, University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro (M.W.-C.); Amyloidosis Center, Boston University School of Medicine (J.L.B.) and Brigham and Women's Hospital, Harvard Medical School (A.M.S., S.D.S.), Boston; Johns Hopkins University, Baltimore (M.P.); Mayo Clinic, Rochester, MN (P.J.D., W.J.L., M.A.G.); University of California, Irvine, Irvine (A.K.W.); Amyloid Network-Hospital Henri Mondor-Assistance Publique-Hôpitaux de Paris (AP-HP)-Université Paris Est, Créteil, France (V.P.-B.); Institute for Neurologic Research Raúl Carrea, FLENI, Buenos Aires (F.A.B.); Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia (G.M., L.O.), and Unit of Neurology, University Hospital, Messina (G.V.) - both in Italy; Hospital AACD (Associação de Assistência à Criança Deficiente), São Paulo (M.S.); Columbia University Medical Center (T.H.B.) and Mount Sinai Medical Center (P.D.G.), New York; University College London-National Amyloidosis Centre, London (C.W.); Penn Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia (B.M.D.); Centre Hospitaliere Universitaire Bicêtre, AP-HP, Unité 1195, INSERM, Université Paris-Sud, Paris (D.A.); Oregon Health and Science University, Portland (S.B.H.); Centro Hospitalar Lisboa Norte-Hospital de Santa Maria, Lisbon (I.C.), and Centro Hospitalar do Porto, Porto (T.C.) - both in Portugal; Universitätsklinikum Münster, Münster, Germany (H.H.S.); Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (J.M.C.), and Hospital Universitari Vall d'Hebron (J.G.), Barcelona; Auckland City Hospital, Auckland, New Zealand (E.G.); and Ionis Pharmaceuticals, Carlsbad, CA (B.P.M., S.G.H., T.J.K., B.W.M., S.W.J., B.F.B., E.J.A.).

Background: Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding transthyretin ( TTR) that induce transthyretin misfolding and systemic deposition of amyloid. Progressive amyloid accumulation leads to multiorgan dysfunction and death. Inotersen, a 2'- O-methoxyethyl-modified antisense oligonucleotide, inhibits hepatic production of transthyretin. Read More

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http://dx.doi.org/10.1056/NEJMoa1716793DOI Listing
July 2018
39 Reads

Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis.

N Engl J Med 2018 07;379(1):11-21

From Assistance Publique-Hôpitaux de Paris (APHP), National Reference Center for Familial Amyloidotic Polyneuropathy, Centre Hospitalier Universitaire (CHU) Bicêtre, INSERM Unité 1195, Université Paris-Sud, Le Kremlin-Bicêtre (D.A.), the Department of Neuromuscular Disorders and ALS, Hôpital de la Timone, Marseille (S.A.), and the Department of Neurology, Amyloid Network, CHU Henri Mondor-APHP, Créteil (V.P.-B.) - all in France; the National Institute of Medical Sciences and Nutrition-Salvador Zubiran, Mexico City (A.G.-D.); the Department of Clinical Research, eStudySite, San Diego, CA (W.D.O.); the Department of Neurology, National Taiwan University Hospital (C.-C.Y.), and the Department of Neurology, Taipei Veterans General Hospital (K.-P.L.), Taipei, Taiwan; Kumamoto University Hospital, Kumamoto (M.U.), and the Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto (Y.S.) - both in Japan; the Department of Cardiology, University of Heidelberg, Heidelberg (A.V.K.), and Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster (H.H.S.) - both in Germany; University Multiprofile Hospital for Active Treatment, Sofia, Bulgaria (I.T.); Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal (T.C.); the Amyloidosis Center, Department of Medicine, Boston Medical Center (J.L.B.), and Harvard Medical School (S.D.S.), Boston; the Department of Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy (G.V.); the Departments of Neurology and Medicine, Vancouver General Hospital, Vancouver, BC, Canada (M.M.M.); the Department of Nephrology, Hospital Clinic, Barcelona (J.M.C.), and the Balearic Islands Health Research Institute and Hospital Son Llatzer, Palma de Mallorca (J.B.) - all in Spain; the Department of Neurology, Columbia University, College of Physicians and Surgeons, New York (T.H.B.); Samsung Medical Center, Sungkyunkwan University School of Medicine (B.J.K.), and the the Department of Neurology, Konkuk University Medical Center (J.O.), Seoul, South Korea; the Department of Neurology, Istanbul University, Istanbul, Turkey (Y.P.); the Division of Medicine, University College London, London (P.N.H.); Johns Hopkins Bayview Medical Center, Baltimore (M.P.); the Department of Neurology, Mayo Clinic, Rochester, MN (P.J.D.); Alnylam Pharmaceuticals, Cambridge, MA (P.J.G., S.G., J.C., A.L.S., S.V.N., M.T.S., P.P.G., A.K.V., J.A.G.); and the Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden (O.B.S.).

Background: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.

Methods: In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks. Read More

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http://www.nejm.org/doi/10.1056/NEJMoa1716153
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http://dx.doi.org/10.1056/NEJMoa1716153DOI Listing
July 2018
25 Reads

Oligonucleotide Drugs for Transthyretin Amyloidosis.

Authors:
Joel N Buxbaum

N Engl J Med 2018 07;379(1):82-85

From the Scripps Research Institute, La Jolla, CA.

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http://dx.doi.org/10.1056/NEJMe1805499DOI Listing
July 2018
7 Reads

Amyloid seeding of transthyretin by ex vivo cardiac fibrils and its inhibition.

Proc Natl Acad Sci U S A 2018 07 28;115(29):E6741-E6750. Epub 2018 Jun 28.

Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095;

Each of the 30 human amyloid diseases is associated with the aggregation of a particular precursor protein into amyloid fibrils. In transthyretin amyloidosis (ATTR), mutant or wild-type forms of the serum carrier protein transthyretin (TTR), synthesized and secreted by the liver, convert to amyloid fibrils deposited in the heart and other organs. The current standard of care for hereditary ATTR is liver transplantation, which replaces the mutant gene with the wild-type gene. Read More

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http://dx.doi.org/10.1073/pnas.1805131115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055172PMC
July 2018
12 Reads

Unusual duplication mutation in a surface loop of human transthyretin leads to an aggressive drug-resistant amyloid disease.

Proc Natl Acad Sci U S A 2018 07 25;115(28):E6428-E6436. Epub 2018 Jun 25.

Amyloidosis Center, Boston University School of Medicine, Boston, MA 02118;

Transthyretin (TTR) is a globular tetrameric transport protein in plasma. Nearly 140 single amino acid substitutions in TTR cause life-threatening amyloid disease. We report a one-of-a-kind pathological variant featuring a Glu51, Ser52 duplication mutation (Glu51_Ser52dup). Read More

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http://dx.doi.org/10.1073/pnas.1802977115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048550PMC
July 2018
18 Reads

Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis.

J Vis Exp 2018 06 9(136). Epub 2018 Jun 9.

Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and Chang Gung University College of Medicine;

Genetic testing is the most reliable test for hereditary transthyretin related amyloidosis and should be performed in most cases of transthyretin amyloidosis (ATTR). ATTR is a rare but fatal disease with heterogeneous phenotypes; therefore, the diagnosis is sometimes delayed. With increasing attention and broader recognition on early manifestations of ATTR as well as emerging treatments, appropriate diagnostic studies, including the transthyretin (TTR) genetic test, to confirm the types and variants of ATTR are therefore fundamental to improve the prognosis. Read More

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http://dx.doi.org/10.3791/57743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101697PMC
June 2018
1 Read

Features of atrial fibrillation in wild-type transthyretin cardiac amyloidosis: a systematic review and clinical experience.

ESC Heart Fail 2018 10 19;5(5):772-779. Epub 2018 Jun 19.

Amyloidosis Center, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA.

Aims: Wild-type transthyretin (ATTRwt) cardiac amyloidosis has emerged as an important cause of heart failure in the elderly. Atrial fibrillation (AF) commonly affects older adults with heart failure and is associated with reduced survival, but its role in ATTRwt is unclear. We sought to explore the clinical impact of AF in ATTRwt. Read More

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http://dx.doi.org/10.1002/ehf2.12308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165925PMC
October 2018

Epigallocatechin-3-gallate tolerability and impact on survival in a cohort of patients with transthyretin-related cardiac amyloidosis. A single-center retrospective study.

Intern Emerg Med 2018 Jun 7. Epub 2018 Jun 7.

Tuscan Regional Amyloid Center, Careggi University Hospital, Florence, Italy.

Transthyretin-related (ATTR) cardiac amyloidosis is currently lacking a disease-modifying therapy. Despite demonstration of effectiveness in halting amyloid deposition, no study focused on epigallocatechin-3-gallate (EGCG) impact on patient survival. We sought to explore prognostic impact of EGCG in a cohort of lone cardiac ATTR patients. Read More

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http://dx.doi.org/10.1007/s11739-018-1887-xDOI Listing
June 2018
7 Reads

Failure of Tafamidis to Halt Progression of Ala36Pro TTR Oculomeningovascular Amyloidosis.

J Stroke Cerebrovasc Dis 2018 Sep 18;27(9):e212-e214. Epub 2018 May 18.

Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy. Electronic address:

Oculomeningovascular amyloidosis is a variant of transthyretin (TTR) amyloidotic polyneuropathy, which is associated with blindness and brain ischemia, microhemorrages, and siderosis due to prominent production of the abnormal TTR in the eye and in the choroid plexuses. Tafamidis is a TTR stabilizer that is orally administered and, by interfering with amyloid fibril formation and deposition, is capable of slowing progression of TTR polyneuropathy and of early-stage cardiomyopathy. However, the ocular manifestations of amyloid deposition progressed despite tafamidis therapy in Val30Met TTR amyloidosis, and the effects of tafamidis on meningovascular amyloidosis are unknown. Read More

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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.04.033DOI Listing
September 2018
1 Read

Musculoskeletal Manifestations of Amyloidosis: A Focused Review.

J Surg Orthop Adv Spring 2018;27(1):1-5

Department of Orthopaedic Surgery, Howard University Hospital, Washington, D.C.

Amyloidosis is a poorly understood condition that can wreak havoc on numerous systems within the human body. In addition, this disease can present in multiple forms which each have their own unique physiology and subsequent effects. However, while the literature on the etiology and effect of amyloidosis on various organ systems is numerous, few have highlighted the musculoskeletal manifestations of this devastating disease. Read More

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July 2018
2 Reads

Diagnostic accuracy of bone scintigraphy in the assessment of cardiac transthyretin-related amyloidosis: a bivariate meta-analysis.

Eur J Nucl Med Mol Imaging 2018 10 23;45(11):1945-1955. Epub 2018 Apr 23.

Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Purpose: Cardiac transthyretin-related amyloidosis (ATTR) is a progressive and fatal cardiomyopathy. The diagnosis of this disease is frequently delayed or missed due to the limited specificity of echocardiography. An increasing amount of data in the literature demonstrate the ability of bone scintigraphy with bone-seeking radiopharmaceuticals to detect myocardial amyloid deposits, in particular in patients with ATTR. Read More

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http://dx.doi.org/10.1007/s00259-018-4013-4DOI Listing
October 2018
12 Reads

The variable phenotype of familial transthyretin-related amyloidosis.

Acta Neurol Belg 2018 Apr 20. Epub 2018 Apr 20.

Laboratory of Experimental and Computational Neuroscience, Department of Biosystems, Federal University of São João del-Rei, São João Del-Rei, Brazil.

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http://dx.doi.org/10.1007/s13760-018-0923-yDOI Listing
April 2018
5 Reads

Characterization of Non-amyloidogenic G101S Transthyretin.

Biol Pharm Bull 2018 ;41(4):628-636

Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences.

Transthyretin (TTR) is a tetrameric beta-sheet-rich protein that is important in the plasma transport of thyroxine and retinol. Mutations in the TTR gene cause TTR tetramer protein to dissociate to monomer, which is the rate-limiting step in familial amyloid polyneuropathy. Amyloidogenicity of individual TTR variants depends on the types of mutation that induce significant changes in biophysical, biochemical and/or biological properties. Read More

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http://dx.doi.org/10.1248/bpb.b17-01021DOI Listing
September 2018
3 Reads

[Transthyretin Familial Amyloid Polyneuropathy - Disease Profile of a Multisystem Disorder].

Dtsch Med Wochenschr 2018 Mar 15;143(6):427-430. Epub 2018 Mar 15.

Transthyretin-related Familial Amyloid Polyneuropathy (ATTR Amyloidosis, former FAP, here called TTR-FAP) is a rare, progressive autosomal dominant inherited amyloid disease ending fatal within 5 - 15 years after final diagnosis. TTR-FAP is caused by mutations of transthyretin (TTR), which forms amyloid fibrils affecting peripheral and autonomic nerves, the heart and other organs. Due to the phenotypic heterogeneity and partly not specific enough clinical symptoms, diagnosis of TTR-FAP can be complicated. Read More

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http://dx.doi.org/10.1055/s-0043-123681DOI Listing
March 2018
7 Reads

Single-centre experience on transthyretin familial amyloid polyneuropathy: case series and literature review.

Acta Neurol Belg 2018 Jun 9;118(2):179-185. Epub 2018 Mar 9.

Department of Neurology and Neuromuscular Reference Centre, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.

Familial amyloid polyneuropathy (FAP) is a most often length-dependent axonal neuropathy, often part of a multisystem disorder also affecting other organs, such as cardiac, gastrointestinal, genitourinary, renal, meningeal and eye tissue. It is most frequently the result of a mutation in the TTR gene, most commonly a p.Val50Met mutation. Read More

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http://dx.doi.org/10.1007/s13760-018-0906-zDOI Listing
June 2018
28 Reads

Cardiac denervation evidenced by MIBG occurs earlier than amyloid deposits detection by diphosphonate scintigraphy in TTR mutation carriers.

Eur J Nucl Med Mol Imaging 2018 07 6;45(7):1108-1118. Epub 2018 Mar 6.

Nuclear Medicine Department, Bichat Claude Bernard Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), DHU FIRE, Inserm UMR-S 1148, Paris Diderot University, Paris, France.

Purpose: Cardiac involvement in familial transthyretin (TTR) amyloidosis is of major prognostic value, and the development of early-diagnostic tools that could trigger the use of new disease-modifying treatments is crucial. The aim of our study was to compare the respective contributions of Tc-diphosphonate scintigraphy (DPD, detecting amyloid deposits) and I-MIBG (MIBG, assessing cardiac sympathetic denervation) in patients with genetically proven TTR mutation referred for the assessment of cardiac involvement.

Methods: We prospectively studied 75 consecutive patients (classified as symptomatic or asymptomatic carriers), using clinical evaluation, biomarkers (troponin and BNP), echocardiography, and nuclear imaging. Read More

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http://dx.doi.org/10.1007/s00259-018-3963-xDOI Listing
July 2018
13 Reads

Analogies and disparities among scintigraphic bone tracers in the diagnosis of cardiac and non-cardiac ATTR amyloidosis.

J Nucl Cardiol 2018 Feb 22. Epub 2018 Feb 22.

Cardiology, DIMES, Alma Mater University of Bologna, Bologna, Italy.

In this issue of JNC, BW Spery and Coll report a retrospective analysis of 57 patients with transthyretin-related amyloidosis (ATTR) in an advanced phase of the disease who underwent 99mTechnetium-pyrophosphate (99mTcPYP) scintigraphy. Although relatively small and "negative," the study is relevant since it broadens our knowledge on the uptake of "bone tracers" in ATTR and contributes to understand the limitations of the clinical use of scintigraphy in this disease. The paper raises, directly or indirectly, at least three questions: To what extent are the different bone tracers interchangeable for the diagnosis of ATTR cardiac amyloidosis? Are bone tracers able to image non-cardiac ATTR amyloidosis? What is the explanation for the variable performance of the different bone tracers in the diagnosis of cardiac and extracardiac ATTR amyloidosis? Read More

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http://dx.doi.org/10.1007/s12350-018-1235-6DOI Listing
February 2018
5 Reads

[Classification of cardiac amyloidosis: an immunohistochemical analysis].

Zhonghua Bing Li Xue Za Zhi 2018 Feb;47(2):105-109

Department of Pathology, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China.

To evaluate the sensitivity and specificity of immunohistochemistry (IHC) in the classification of cardiac amyloidosis on endomyocardial biopsy (EMB) and heart allograft. Twenty cardiac tissues from 19 patients at Fuwai Hospital from January, 1990 to April, 2017 with histopathologic features of amyloidosis and Congo red staining positivity were included. IHC was performed with monoclonal antibodies against AA amyloid and polyclonal antibodies against transthyretin (ATTR), λ-light chain (AL-λ), κ-light chain (AL-κ), ApoAⅠ, ApoAⅡ, ApoA Ⅳ and β(2)-microglobin. Read More

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http://dx.doi.org/10.3760/cma.j.issn.0529-5807.2018.02.005DOI Listing
February 2018
4 Reads

Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR).

Amyloid 2018 Mar 9;25(1):62-67. Epub 2018 Feb 9.

a Amyloidosis Center , Boston University School of Medicine , Boston , MA , USA.

Objective: To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin (ATTR) amyloidosis.

Patients And Methods: We performed a retrospective analysis of patients with biopsy-proven ATTRwt (wild-type transthyretin amyloid protein) and genopositive ATTR V122I (valine-to-isoleucine substitution at position 122 of the TTR gene) amyloidosis evaluated at the Amyloidosis Center at Boston University and Boston Medical Center between 1 January 2003 and 31 December 2016.

Results: There were a total of 226 patients with ATTRwt and ATTR V122I amyloidosis evaluated during the specified time frame with 155 and 71 patients in each cohort, respectively. Read More

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http://dx.doi.org/10.1080/13506129.2018.1436048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157907PMC
March 2018
5 Reads

Normal scores of deep breathing tests: beware of dysrhythmia in transthyretin amyloidosis.

Amyloid 2018 Mar 2;25(1):54-61. Epub 2018 Feb 2.

c Department of Surgical and Perioperative Sciences, Clinical Physiology, Heart Centre , Umeå University , Umeå , Sweden.

Background: The heart rate (HR) response to paced deep breathing (DB) is a common test of cardiac autonomic function, where high heart rate variability (HRV) is considered to reflect normal autonomic function. We evaluated the DB test in patients with hereditary transthyretin amyloid (ATTRm) amyloidosis, where autonomic dysregulation and atrial arrhythmias are common.

Methods: Paced DB was performed during one minute (six breaths/min) in 165 recordings in adult ATTRm amyloidosis patients with the TTR Val30Met mutation, 42 hypertrophic cardiomyopathy (HCM) patients and 211 healthy subjects. Read More

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http://dx.doi.org/10.1080/13506129.2018.1434140DOI Listing
March 2018
6 Reads

On-a-chip tryptic digestion of transthyretin: a step toward an integrated microfluidic system for the follow-up of familial transthyretin amyloidosis.

Analyst 2018 Feb;143(5):1077-1086

Faculté de Pharmacie, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.

A microfluidic microreactor for trypsin mediated transthyretin (TTR) digestion has been developed as a step towards the elaboration of a fully integrated microdevice for the detection of a rare and disabling disease, the familial transthyretin amyloidosis (ATTR) which is related to specific TTR mutations. Therefore, an enzymatic microreactor coupled to an analytical step able to monitor the mutation of TTR on specific peptide fragments would allow an accurate monitoring of the treatment efficiency of ATTR. In this study, two types of immobilized trypsin microreactors have been investigated: a new miniaturized, microfluidic fluidized bed packed with trypsin functionalized magnetic particles (MPs), and a thiol-ene (TE) monolith-based chip. Read More

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http://dx.doi.org/10.1039/c7an01737eDOI Listing
February 2018
109 Reads

Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis.

Amyloid 2018 Mar 25;25(1):46-53. Epub 2018 Jan 25.

a Public Health and Clinical Medicine , Umeå University , Umeå , Sweden.

Background: Cardiac amyloidosis (CA) is a myocardial disease and commonly under-diagnosed condition. In CA patients, atrial fibrillation might occur in the absence of left atrial (LA) enlargement.

Objectives: The aim of this study is to assess LA size and function, and its relationship with atrial arrhythmia in patients with hereditary transthyretin amyloidosis (ATTR). Read More

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http://dx.doi.org/10.1080/13506129.2018.1430027DOI Listing
March 2018
11 Reads

Psychopathological dimensions in subjects with hereditary ATTR V30M amyloidosis and their relation with life events due to the disease.

Amyloid 2018 Mar 22;25(1):26-36. Epub 2018 Jan 22.

a Serviço de Psiquiatria e Saúde Mental , Centro Hospitalar do Porto , Porto , Portugal.

Background: Chronic physical illness has been associated with emotional distress. Chronic diseases may change usual family patterns with economic, social and family losses. Hereditary ATTR V30M amyloidosis is a rare, fatal inherited systemic amyloidosis, with chronic evolution and beginning in adulthood. Read More

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http://dx.doi.org/10.1080/13506129.2018.1428795DOI Listing
March 2018
6 Reads

Hydroxychloroquine-Mediated Cardiotoxicity With a False-Positive Technetium-Labeled Pyrophosphate Scan for Transthyretin-Related Cardiac Amyloidosis.

Circ Cardiovasc Imaging 2018 Jan;11(1)

From the Departments of Cardiovascular Diseases (I.C.Y.C., J.P.B., M.G.), Pathology (M.C.B., J.J.M.), and Radiology and Immunology (G.B.J.), Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1161/CIRCIMAGING.117.007059DOI Listing
January 2018
4 Reads

Oculoleptomeningeal Amyloidosis Secondary to the Rare Transthyretin c.381T>G (p.Ile127Met) Mutation.

World Neurosurg 2018 Mar 23;111:190-193. Epub 2017 Dec 23.

Division of Neurosurgery, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: Oculoleptomeningeal amyloidosis (OLMA) represents a rare subtype of familial transthyretin (TTR) amyloidosis, characterized by deposition of amyloid in cranial and spinal leptomeninges along with ocular involvement. Of >100 TTR mutations identified, few have been associated with OLMA. Herein we describe the first report of leptomeningeal amyloidosis associated with the c. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S18788750173221
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http://dx.doi.org/10.1016/j.wneu.2017.12.096DOI Listing
March 2018
12 Reads

Transthyretin amyloidosis in a septuagenarian masquerading as hypertrophic cardiomyopathy: the importance of multimodality imaging.

Eur Heart J Cardiovasc Imaging 2018 03;19(3):328

Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Centers, University of Wisconsin School of Medicine and Public Health, 2801 W. Kinnickinnic River Parkway, Milwaukee, WI 53215, USA.

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http://dx.doi.org/10.1093/ehjci/jex329DOI Listing
March 2018
8 Reads

quantification of amyloid burden in TTR-related cardiac amyloidosis.

Intractable Rare Dis Res 2017 Nov;6(4):291-294

Department of Internal Medicine I - Cardiology, RWTH Aachen University, Germany.

Cardiac transthyretin-related (ATTR) amyloidosis is a severe cardiomyopathy for which therapeutic approaches are currently under development. Because non-invasive imaging techniques such as cardiac magnetic resonance imaging and echocardiography are non-specific, the diagnosis of ATTR amyloidosis is still based on myocardial biopsy. Thus, diagnosis of ATTR amyloidosis is difficult in patients refusing myocardial biopsy. Read More

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http://dx.doi.org/10.5582/irdr.2017.01065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735283PMC
November 2017
9 Reads

Cardiac amyloidosis: An update on diagnosis and treatment.

Cleve Clin J Med 2017 Dec;84(12 Suppl 3):12-26

Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.

Cardiac amyloidosis (CA), once thought to be a rare disease, is increasingly recognized due to enhanced clinical awareness and better diagnostic imaging. CA is becoming of heightened interest to the cardiology community given more effective treatment strategies for light chain amyloidosis (AL), as well as emerging therapies for transthyretin amyloidosis (ATTR). Furthermore, reversing amyloid deposition in affected organs using monoclonal antibodies is actively being tested in clinical trials. Read More

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http://dx.doi.org/10.3949/ccjm.84.s3.02DOI Listing
December 2017
13 Reads

Reply.

Am J Ophthalmol 2018 02 13;186:170. Epub 2017 Dec 13.

Rochester, Minnesota.

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http://dx.doi.org/10.1016/j.ajo.2017.11.005DOI Listing
February 2018
9 Reads

Coronary ectasia in amyloid cardiomyopathy and neuropathy due to the transthyretin mutation c.323A>G.

Heart Lung 2018 Mar - Apr;47(2):127-129. Epub 2017 Dec 13.

2nd Medical Department with Cardiology and Intensive Care Medicine, Krankenanstalt Rudolfstiftung, Vienna, Austria.

Background: atrial fibrillation(AF) is a frequent manifestation of cardiac involvement in genetic and wild-type transthyretin-related familial amyloidosis(TTR-FA). However, ectasia of coronary arteries and ablation for AF have not been reported in TTR-FA.

Methods And Results: A 65yo male developed progressive sensori-motor polyneuropathy since age 59y. Read More

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http://dx.doi.org/10.1016/j.hrtlng.2017.11.007DOI Listing
December 2018
6 Reads