Distinct characteristics of amyloid deposits in early- and late-onset transthyretin Val30Met familial amyloid polyneuropathy

Koike, Haruki; Ando, Yumiko; Ueda, Mitsuharu; Kawagashira, Yuichi; Iijima, Masahiro; Fujitake, Junko; Hayashi, Manabu; Yamamoto, Masahiko; Mukai, E; Nakamura, Tomohiko; Katsuno, Masahisa; Hattori, Naoki; Sobue, Gen

doi:10.1016/j.jns.2009.07.028

Cited by 93 publications

(89 citation statements)

References 39 publications

(64 reference statements)

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“…The deposits are mainly located within or around endoneurial or perineurial vessel walls, especially in Val107 patients in our study, in keeping with previous reports 42. Contrary to early onset Met30 patients,36, 43 amyloid deposits are sparse in non‐Portuguese patients, necessitating careful histopathological examination in reference centers with examination of all sections. As in our series, amyloid deposits were found in most reported cases, often after second‐look examination, repeat biopsy, or necropsy (see Supplementary Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…Scarce amyloid deposition casts doubt on the pathogenicity of these deposits. Axonal degeneration starts long before the first deposits, which are composed of both mutant and wild‐type TTR protein 43. Nonfibrillary mutant and wild‐type TTR appear to lead to inflammation and oxidative stress, followed by axonal degeneration and neuronal loss even before deposits appear 6, 44.…”

Section: Discussionmentioning

confidence: 99%

“…Amyloid deposition in conduction pathways requiring pacemaker implantation was also more frequent in non‐Portuguese than PortMet30 patients (see Table 3). A higher prevalence of severe cardiac infiltration in LateMet30 may reflect more diffuse myocardial amyloid deposition, leading to frequent pacemaker requirement 36, 43, 46…”

Section: Discussionmentioning

confidence: 99%

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Genotype–phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France

Mariani¹,

Lozeron

Théaudin

et al. 2015

Annals of Neurology

146

102

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ObjectiveTo compare the natural history of familial transthyretin amyloid polyneuropathies (FAP) due to the Val30Met, Ser77Tyr, and Ile107Val mutations in France with the classical Portuguese Val30Met FAP.MethodsWe compared 84 French patients with a control group of 110 Portuguese patients carrying the Val30Met mutation also living in France, all referred to and followed at the French National FAP Reference Center from 1988 to 2010. Clinical examination, functional and walking disability scores, nerve conduction studies, and muscle biopsies are reported. We also conducted a comprehensive literature review to further determine the range of phenotypic expression.ResultsBy comparison with Portuguese Val30Met FAP, French Ile107Val, Ser77Tyr, and LateVal30Met FAP showed more rapid and severe disease progression; onset of gait disorders was 3 times more rapid (p < 0.0001) and the rate of modified Norris test decline was up to 40 times faster in Ile107Val patients (p < 0.0001). Median survival was much shorter in Ile107Val and in Val30Met mutation with late onset (>50 years; LateMet30) FAP (p = 0.0005). Other distinctive features relative to the Portuguese patients included atypical clinical presentations, demyelination on nerve conduction studies (p = 0.0005), and difficult identification of amyloid deposits in nerve and muscle biopsies.InterpretationIle107Val and LateMet30 mutations are associated with the most debilitating and severe FAP ever described, with rapid onset of tetraparesis and shorter median survival. It could be explained by frequent large‐fiber involvement and associated demyelination and more severe axonal loss. These findings have major implications for genetic counseling and patient management as new therapeutic options are being assessed in clinical trials (TTR gene silencing). Ann Neurol 2015;78:901–916

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genotype–phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France

Mariani¹,

Lozeron

Théaudin

et al. 2015

Annals of Neurology

146

102

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“…In FAP with ATTRVal30Met it has been shown that the clinical picture and the histopathological and electrophysiological findings of peripheral nerve lesions are considerably different between patients with early-onset type and those with late-onset type [10,[15][16][17]: the latter group of patients frequently has serious cardiac involvement [37], and upper limb neuropathy may develop at an earlier stage of the disease than previously recognized [38,39]. Histopathology of dorsal root ganglia shows a more selective loss of small neurons in early-onset patients [40], while loss of neurons of all sizes is seen in late-onset patients [15].…”

Section: Difference In Pathophysiology Between Endemic-versus Non-endmentioning

confidence: 99%

“…An anticipation phenomenon is also observed only in endemic patients [11][12][13][14]. It was recently shown that histopathological and electrophysiological Kodaira et al 4 of 26 findings of peripheral nerve lesions differed between the two groups [15][16][17]. Although genetic, gender and environmental factors, and aging are surmised to be the causes of these differences, the details remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological features of familial amyloid polyneuropathy in endemic area

Kodaira

Morita

Shimojima

et al. 2011

Amyloid

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The process of deterioration of peripheral nerve function in familial amyloid polyneuropathy (FAP) with amyloidogenic transthyretin (ATTR) Val30Met has not been systematically evaluated hitherto. We performed nerve conduction studies in 69 patients with FAP with ATTR Val30Met from one of the endemic areas in Japan. Sensory conduction velocity (SCV), motor conduction velocity (MCV), the size of the compound muscle action potential (CMAP), and distal latency (DL) were measured in the ulnar and tibial nerves. SCV was evaluated using the orthodromic method with needle recording electrodes. These electrophysiological parameters were compared with clinical stage of FAP and duration of neuropathy. When subjects noted minimal neuropathic symptoms only in the feet, motor and sensory nerve function in both the hands and feet had already been disturbed. Sensory nerve action potential on the foot disappeared more rapidly than CMAP. CMAP on foot muscle rapidly decreased during the initial 2 years and completely disappeared within 10 years. The duration of illness and deterioration parameters (CMAP of the abductor minimi muscle, MCV and SCV of the ulnar nerve, and DL of both ulnar and tibial nerves) were linearly correlated. CMAP was the most sensitive and reliable parameter to evaluate motor nerve degeneration in FAP.

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Monitoring treatment response to tafamidis by serial native T1 and extracellular volume in transthyretin amyloid cardiomyopathy

et al. 2018

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Tafamidis meglumine, a transthyretin (TTR) stabilizer, is effective in delaying the progression of neuropathy in TTR amyloidosis with Val30Met mutations. However, its efficacy in TTR amyloid cardiomyopathy is not fully elucidated. Herein, we report a 73‐year‐old Japanese man with a diagnosis of TTR amyloid cardiomyopathy with Val30Met mutation treated with tafamidis. To evaluate treatment response, cardiac magnetic resonance imaging was performed before and after 12 months of tafamidis treatment. Native T1, extracellular volume, and left ventricular mass showed no obvious worsening, and findings of other diagnostic studies also supported the efficacy of tafamidis to delay the progression of amyloid cardiomyopathy. Our case suggests that serial native T1 and extracellular volume may be novel non‐invasive imaging methods to monitor the treatment response to TTR stabilizers in cardiac amyloidosis and also that tafamidis may be effective in suppressing cardiac progression in TTR amyloid cardiomyopathy with Val30Met mutation.

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Distinct characteristics of amyloid deposits in early- and late-onset transthyretin Val30Met familial amyloid polyneuropathy

Cited by 93 publications

References 39 publications

Genotype–phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France

Genotype–phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France

Electrophysiological features of familial amyloid polyneuropathy in endemic area

Monitoring treatment response to tafamidis by serial native T1 and extracellular volume in transthyretin amyloid cardiomyopathy

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