Amiloidosi da transtiretina (ATTR): l’altra faccia della medaglia

2019 ◽  
Vol 31 (1) ◽  
pp. 12-21
Author(s):  
Federico Perfetto ◽  
Francesco Cappelli ◽  
Silvia Farsetti ◽  
Elio Dimarcantonio ◽  
Silvia Casagrande ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Amyloid Fibrils ◽  
Clinical Symptoms ◽  
Systemic Amyloidosis ◽  
Transthyretin Amyloidosis ◽  
Senile Systemic Amyloidosis ◽  
Intact Molecule ◽  
Total Body ◽  
The Many ◽  
Therapeutic Alternatives

Transthyretin amyloidosis (ATTR) is becoming an emerging clinical entity, and is currently the most common form of systemic amyloidosis. ATTR consists of two distinct diseases depending on whether the amyloid fibrils derive from the intact molecule of TTR (ATTR wild-type or senile systemic amyloidosis) or from different mutations occurred in the TTR molecule gene (ATTRm). Total-body scintigraphy with diphosphonates has greatly improved the diagnosis in patients with isolated cardiac involvement for both ATTRm and ATTRwt, thus avoiding the need of endomiocardial biopsy in cases without serum and/or urinary monoclonal component (MC). Heart failure alone, or associated with peripheral and autonomic neuropathy, are the main clinical symptoms in these patients. Particular attention must be paid in order to exclude hypertrophic cardiomiopathy or light chain (AL) forms in patients with MC. Today, besides hepatic transplantation, which is almost reserved to patients with early Val30Met neuropathy, many new therapeutic alternatives can be offered to these patients. Tafamidis, a TTR-stabilizer that has recently proved to be effective in cardiac forms of both ATTRm and ATTRwt, is now ready for clinical use. In addition, drugs silencing the TTR messenger RNA should soon be available for treatment. The many therapeutic opportunities available today for ATTR, strenghten even more the need for an early diagnosis of the disease both in ATTRm and ATTRwt.

scholarly journals ASFMR1splice variant

2018 ◽  
Vol 4 (4) ◽  
pp. e246 ◽  
Author(s):  
Padmaja Vittal ◽  
Shrikant Pandya ◽  
Kevin Sharp ◽  
Elizabeth Berry-Kravis ◽  
Lili Zhou ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Splice Variant ◽  
Messenger Rna ◽  
Clinical Symptoms ◽  
Fragile X ◽  
Cgg Repeat ◽  
Men And Women ◽  
Fragile X Mental Retardation ◽  
Repeat Size ◽  
Ataxia Syndrome

ObjectiveTo explore the association of a splice variant of theantisense fragile X mental retardation 1(ASFMR1) gene, loss offragile X mental retardation 1(FMR1) AGG interspersions andFMR1CGG repeat size with manifestation, and severity of clinical symptoms of fragile X-associated tremor/ataxia syndrome (FXTAS).MethodsPremutation carriers (PMCs) with FXTAS, without FXTAS, and normal controls (NCs) had a neurologic evaluation and collection of skin and blood samples. Expression ofASFMR1transcript/splice variant 2 (ASFMR1-TV2), nonsplicedASFMR1, totalASFMR1, andFMR1messenger RNA were quantified and compared using analysis of variance. Least absolute shrinkage and selection operator (LASSO) logistic regression and receiver operating characteristic analyses were performed.ResultsPremutation men and women both with and without FXTAS had higherASFMR1-TV2 levels compared with NC men and women (n = 135,135,p< 0.0001), andASFMR1-TV2 had good discriminating power for FXTAS compared with NCs but not for FXTAS from PMC. After adjusting for age, loss of AGG, larger CGG repeat size (in men), and elevatedASFMR1-TV2 level (in women) were strongly associated with FXTAS compared with NC and PMC (combined).ConclusionsThis study found elevated levels ofASFMR1-TV2and loss of AGG interruptions in both men and women with FXTAS. Future studies will be needed to determine whether these variables can provide useful diagnostic or predictive information.

scholarly journals Clinical features and survival in senile systemic amyloidosis: comparison to familial transthyretin cardiomyopathy

Amyloid ◽  
2011 ◽  
Vol 18 (sup1) ◽  
pp. 157-159 ◽  
Author(s):  
L. H. Connors ◽  
G. Doros ◽  
F. Sam ◽  
A. Badiee ◽  
D. C. Seldin ◽  
...  
Keyword(s):  
Clinical Features ◽  
Systemic Amyloidosis ◽  
Senile Systemic Amyloidosis

Methods to study the structure of misfolded protein states in systemic amyloidosis

2021 ◽  
Vol 49 (2) ◽  
pp. 977-985
Author(s):  
Marcus Fändrich ◽  
Matthias Schmidt
Keyword(s):  
Protein Misfolding ◽  
Amyloid Fibrils ◽  
Ex Vivo ◽  
Systemic Amyloidosis ◽  
Structural Basis ◽  
Amyloid A ◽  
Serum Amyloid A Protein ◽  
Proteolytic Stability

Systemic amyloidosis is defined as a protein misfolding disease in which the amyloid is not necessarily deposited within the same organ that produces the fibril precursor protein. There are different types of systemic amyloidosis, depending on the protein constructing the fibrils. This review will focus on recent advances made in the understanding of the structural basis of three major forms of systemic amyloidosis: systemic AA, AL and ATTR amyloidosis. The three diseases arise from the misfolding of serum amyloid A protein, immunoglobulin light chains or transthyretin. The presented advances in understanding were enabled by recent progress in the methodology available to study amyloid structures and protein misfolding, in particular concerning cryo-electron microscopy (cryo-EM) and nuclear magnetic resonance (NMR) spectroscopy. An important observation made with these techniques is that the structures of previously described in vitro formed amyloid fibrils did not correlate with the structures of amyloid fibrils extracted from diseased tissue, and that in vitro fibrils were typically more protease sensitive. It is thus possible that ex vivo fibrils were selected in vivo by their proteolytic stability.

Arterial thromboembolism in senile systemic amyloidosis: report of two cases

Amyloid ◽  
2012 ◽  
Vol 19 (2) ◽  
pp. 118-121 ◽  
Author(s):  
Michitaka Nakagawa ◽  
Kana Tojo ◽  
Yoshiki Sekijima ◽  
Kyo-hei Yamazaki ◽  
Shu-ichi Ikeda
Keyword(s):  
Systemic Amyloidosis ◽  
Arterial Thromboembolism ◽  
Senile Systemic Amyloidosis

Transthyretin-assoziierte familiäre Amyloidpolyneuropathie

2018 ◽  
Vol 143 (06) ◽  
pp. 427-430
Author(s):  
Christoph Niemietz ◽  
Christoph Röcken ◽  
Matthias Schilling ◽  
Jörg Stypman ◽  
Constantin Uhlig ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Clinical Symptoms ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Correct Diagnosis ◽  
Vitreous Body ◽  
Final Diagnosis ◽  
Autonomic Nerves ◽  
Loss Of Weight ◽  
Peripheral Polyneuropathy ◽  
Immunohistochemical Evidence

AbstractTransthyretin-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. False diagnoses can include idiopathic polyneuropathy, chronic inflammatory demyelinating polyneuropathy, diabetic neuropathy as well as paraneoplastic syndrome. Hence, it is assumed that many cases remain unreported. Early and correct diagnosis of TTR-FAP is crucial, since appropriate therapeutic options exist. TTR-FAP should always be differentially diagnosed, when apart from a progressive peripheral polyneuropathy, additional symptoms as autonomic dysfunction, cardiomyopathy, gastrointestinal disorders, unexpected loss of weight, carpal tunnel syndrome, restrictions of renal function, epileptic fits, and corneal and vitreous body clouding occur. Histological evidence of amyloid and successive immunohistochemical evidence of transthyretin as well as genetic testing for transthyretin mutations, lead to an accurate diagnosis.

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