Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease

Adams, David H.; Koike, Haruki; Slama, Michel; Coelho, Teresa

doi:10.1038/s41582-019-0210-4

Cited by 290 publications

(421 citation statements)

References 184 publications

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“…French late‐onset Val30Met patients also reported similar clinical characteristics to Japanese late‐onset Val30Met patients . These late‐onset Val30Met cases are now prevalent throughout the world …”

Section: Clinical Featuresmentioning

confidence: 56%

“…17 These late-onset Val30Met cases are now prevalent throughout the world. 1,18 Clinical differences between the early-and late-onset ATTR Val30Met amyloidosis cases have also been reported in other countries. 17,19,20 Although patients from conventional endemic foci of Japan and Portugal exhibit similar age at disease onset and clinical features, Swedish patients tend to manifest the age at onset and clinical features similar to the late-onset cases from non-endemic areas.…”

Section: Clinic Al Fe Ature Smentioning

confidence: 64%

“…51 More recently, siRNA and ASO that suppress production of both the wild-type and variant TTR from the liver have been introduced as possible therapeutic options for treating ATTRv amyloidosis. 1 In 2018, the results of phase III clinical trials of intravenously administrated siRNA, patisiran, and subcutaneously administrated ASO, inotersen, were published. 8,9 As both studies achieved their primary endpoints, these gene-silencing drugs seem to be the most optimal treatment for ATTRv amyloidosis if the long-term efficacy and tolerability are confirmed.…”

Section: Recent Advan Ce S In the Tre Atmentmentioning

confidence: 99%

“…TTR is a transport protein primarily synthesized in the liver, retinal pigment epithelium in the eye, and choroid plexus in the brain. 1 Wild-type TTR is a stable homotetramer and functions as a thyroxin and retinol (vitamin A)-binding protein transporter, whereas variant TTR tends to induce dissociation of the TTR tetramer into monomers, causing the deposition of amyloid fibrils in the extracellular spaces. 2,3 ATTRv amyloidosis was initially reported in Portugal and subsequently in the restricted areas of Japan and Sweden.…”

Section: Introductionmentioning

confidence: 99%

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Clinicopathological spectrum and recent advances in the treatment of hereditary transthyretin amyloidosis

Koike

Fukami

Nishi

et al. 2019

Neurology & Clinical Neurosc

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Hereditary transthyretin (ATTRv) amyloidosis, also known as familial amyloid polyneuropathy, is a disease caused by the systemic deposition of variant transthyretin (TTR). Although this disease was primarily indigenous to endemic foci in Portugal, Japan, and Sweden, its prevalence has increased throughout the world. The clinical phenotypes of ATTRv amyloidosis are diverse, including neuropathy, cardiomyopathy, and oculoleptomeningeal involvement as the predominant features, depending on the mutation type and age of onset. Val30Met, one of the most common TTR mutations, exhibits varying characteristic features in the early‐onset patients from conventional endemic foci and the late‐onset patients from non‐endemic areas. Autonomic dysfunctions and dissociated sensory loss are the characteristic features of the former, whereas motor dysfunctions and loss of all sensory modalities are conspicuous in the latter. Distortion and atrophy of the Schwann cells due to the formation of amyloid fibrils seem to cause predominant small‐fiber loss in the early‐onset patients, while other mechanisms, such as microangiopathy and the toxicity of TTR oligomers, may contribute to nerve fiber loss in the late‐onset patients. In addition to liver transplantation, novel and less invasive disease‐modifying therapies, such as TTR stabilizers, short interfering RNA, and antisense oligonucleotide, have been shown to be effective in ATTRv amyloidosis patients. Given their ability to ameliorate ATTRv amyloidosis, early diagnosis and treatment are required. Physicians should be aware of the diversity in ATTRv amyloidosis because this disease can be misdiagnosed with other diseases such as chronic inflammatory demyelinating polyneuropathy and immunoglobulin light‐chain amyloidosis.

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Section: Clinical Featuresmentioning

confidence: 56%

Section: Clinic Al Fe Ature Smentioning

confidence: 64%

Section: Recent Advan Ce S In the Tre Atmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Clinicopathological spectrum and recent advances in the treatment of hereditary transthyretin amyloidosis

Koike

Fukami

Nishi

et al. 2019

Neurology & Clinical Neurosc

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“…Hereditary ATTR amyloidosis is an autosomal dominant, systemic disease that usually presents with progressive neuropathy and/or cardiomyopathy and is caused by mutations in the gene that encode transthyretin [1]. Over 130 pathogenic mutations in this gene have been identified and hence, the disease is characterized by a large phenotypic heterogeneity regarding onset and progression [1].…”

mentioning

confidence: 99%

Regression of cardiac amyloid load documented by cardiovascular magnetic resonance in a patient with hereditary amyloidosis

et al. 2020

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Cardiomyopathy correlates to nerve damage in p.A117S late‐onset transthyretin amyloid polyneuropathy

Lin

Hsueh

et al. 2022

Ann Clin Transl Neurol

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Objective Late‐onset hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN) is often associated with heart involvement. Recent advances in cardiac imaging allow the detection of cardiac amyloidosis. This study aimed to explore cardiomyopathy by cardiac imaging and its clinical correlates with polyneuropathy in late‐onset ATTRv‐PN. Methods Polyneuropathy was assessed by intraepidermal nerve fiber (IENF) density, nerve conduction study (NCS), autonomic function tests, quantitative sensory testing, and clinical questionnaires. Cardiomyopathy was evaluated by echocardiography, 99m Tc‐pyrophosphate (PYP) single‐photon emission computed tomography (SPECT) imaging, cardiac magnetic resonance imaging (CMR), and serum Pro‐B‐type natriuretic peptide. Healthy controls and patients with Brugada syndrome were enrolled for comparison of CMR. Results Fifty late‐onset ATTRv‐PN patients (38 men, 46 with p. A117S mutation), aged 63.7 ± 5.5 years, of polyneuropathy disability stage 1–4 were enrolled. All patients presented polyneuropathy in NCS, and 74.5% of patients had reduced IENF density in distal legs. All patients showed significant radiotracer uptake in the heart on 99m Tc‐PYP SPECT imaging, and 87.8% of patients had abnormally increased left ventricular (LV) septum thickness on echocardiography. CMR showed longer myocardial native T1, larger extracellular volume, greater LV mass index, and higher LV mass to end‐diastolic volume ratio in ATTRv‐PN patients than healthy controls and patients with Brugada syndrome. These CMR parameters were associated with skin denervation, absent sympathetic skin responses, elevated thermal thresholds, worsened NCS profiles, and functional deficits of polyneuropathy. Interpretation Late‐onset ATTRv‐PN coexisted with cardiomyopathy regardless of the clinical severity of polyneuropathy. The cardiac amyloid burden revealed by CMR was correlated with pathophysiology and clinical disability of nerve degeneration.

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Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease

Cited by 290 publications

References 184 publications

Clinicopathological spectrum and recent advances in the treatment of hereditary transthyretin amyloidosis

Clinicopathological spectrum and recent advances in the treatment of hereditary transthyretin amyloidosis

Regression of cardiac amyloid load documented by cardiovascular magnetic resonance in a patient with hereditary amyloidosis

Cardiomyopathy correlates to nerve damage in p.A117S late‐onset transthyretin amyloid polyneuropathy

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