Type I (Transthyretin Met30) Familial Amyloid Polyneuropathy in Japan

Koike, Haruki; Misu, Ken Ichiro; Ikeda, Shu Ichi; Ando, Yukio; Nakazato, Masamitsu; Ando, Eiko; Yamamoto, Masahiko; Hattori, Naoki; Sobue, Gen

doi:10.1001/archneur.59.11.1771

Cited by 220 publications

(217 citation statements)

References 27 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…Sensory dissociation was less frequent in the non‐Portuguese patients, as previously reported,33 particularly in those with Tyr77 FAP (see Table 2). In most cases, all fibers were involved at the first examination.…”

Section: Discussionsupporting

confidence: 82%

“…Apart from these studies, patient disability has rarely been documented, especially with respect to gait disorders and overall survival, ruling out any direct statistical comparison of times to onset. This may explain discrepancies in the severity of Tyr77 and LateMet30 FAP in previous reports31, 32, 33 and in our series, in which the median times to assisted walking were longer in Tyr77 than in LateMet30 FAP.…”

Section: Discussioncontrasting

confidence: 69%

“…Initial symptoms such as weakness in Val107 FAP and gait disorders in both Tyr77 and Val107 FAP were never seen in PortMet30 FAP, reflecting the early initial severity of these forms, as previously reported in LateMet30 FAP 33. In the literature, initial symptoms consist mostly of sensory disorders or sometimes weakness, autonomic symptoms, or cardiomyopathy, especially in LateMet30.…”

Section: Discussionsupporting

confidence: 67%

“…Almost all our patients exhibited autonomic dysfunction, as previously reported. Autonomic symptoms are less severe in LateMet30 FAP, accounting less for disability than tetraparesis or cardiomyopathy, as previously reported 31, 33, 36. These differences could be explained by less abundant amyloid deposits and less severe neuron loss in sympathetic than dorsal root ganglia, as previously suggested by a histopathological study of Japanese LateMet30 FAP 36…”

Section: Discussionsupporting

confidence: 64%

“…Weakness occurred early and was severe and extensive in Val107 and LateMet30 FAP, some patients presenting with upper limb involvement or tetraparesis with a proximodistal distribution at the first examination, whereas weakness occurs late and remains limited to the lower limbs in early Met30 8, 9, 33…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

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

Mariani¹,

Lozeron

Théaudin

et al. 2015

Annals of Neurology

146

102

View full text Add to dashboard Cite

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

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussioncontrasting

confidence: 69%

Section: Discussionsupporting

confidence: 67%

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

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

Mariani¹,

Lozeron

Théaudin

et al. 2015

Annals of Neurology

146

102

View full text Add to dashboard Cite

show abstract

Biophysical characterization and modulation of Transthyretin Ala97Ser

Liu

Yen

Ricardo

et al. 2019

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveAla97Ser (A97S) is the major transthyretin (TTR) mutation in Taiwanese patients of familial amyloid polyneuropathy (FAP), characterized by a late‐onset but rapidly deteriorated neuropathy. Tafamidis can restore the stability of some mutant TTR tetramers and slow down the progression of TTR‐FAP. However, there is little understanding of the biophysical features of A97S‐TTR mutant and the pharmacological modulation effect of tafamidis on it. This study aims to delineate the biophysical characteristics of A97S‐TTR and the pharmacological modulation effect of tafamidis on this mutant.MethodThe stability of TTR tetramers was assessed by urea denaturation and differential scanning calorimetry. Isothermal titration calorimetry (ITC) was used to measure the binding constant of tafamidis to TTR. Nuclear magnetic resonance spectroscopy (NMR) titration experiment was used to map out the tafamidis binding site.ResultsChemical and thermal denaturation confirmed the destabilization effect of A97S. Consistent with other the amyloidogenic mutant, A97S‐TTR has slightly lower conformational stability. NMR revealed the binding site of A97S‐TTR with tafamidis is at the thyroxine binding pocket. The ITC experiments documented the high affinity of the binding which can effectively stabilize the A97S‐TTR tetramer.InterpretationThis study confirmed the structural modulation effect of tafamidis on A97S‐TTR and implied the potential therapeutic benefit of tafamidis for A97S TTR‐FAP. This approach can be applied to investigate the modulation effect of tafamidis on other rare TTR variants and help to make individualized choices of available treatments for FAP patients.

show abstract

Clinical and genetic profiles of hereditary transthyretin amyloidosis in Taiwan

Chao

Liao

Liu

et al. 2019

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective The clinical and genetic profiles of hereditary transthyretin amyloidosis ( ATTR ) in Chinese populations remain elusive. We aim to characterize the features of ATTR in a Taiwanese cohort of Han Chinese descent. Methods Seventy‐nine patients with molecularly confirmed ATTR from 57 Taiwanese families were identified by sequencing the transthyretin gene ( TTR ). The clinical and electrophysiological data were scrutinized. Cardiac involvement of ATTR was evaluated by echocardiography and cardiac scintigraphy. Four microsatellite and seven single‐nucleotide polymorphism markers flanking TTR were genotyped to investigate the founder effect of the TTR Ala97Ser mutation. Results Most of the patients had a peripheral neuropathy with variable autonomic symptoms. The average age at disease onset ( AO ) was 58.2 ± 7.2 years, and the male patients had an earlier AO than female patients (56.6 ± 5.7 years vs. 61.8 ± 8.9 years, P = 0.013). Electrophysiological studies revealed a generalized axonal sensorimotor polyneuropathy and isolated median neuropathy in 84.5% and 15.5% of the patients, respectively. Up to 80% of the patients with ATTR had symptomatic or subclinical cardiac involvement. Six TTR mutations were identified in the participants including one novel mutation Glu89Asp. Among them, Ala97Ser was the most common mutation, accounting for 91.2% of the ATTR pedigrees. Detailed haplotype analyses demonstrated a shared haplotype in the 47 patients with the Ala97Ser mutation, suggesting a founder effect. Interpretation The present study delineates the distinct features of ATTR in Taiwan and provides useful information for the diagnosis and management of ATTR , especially in patients of Chinese descent.

show abstract

Type I (Transthyretin Met30) Familial Amyloid Polyneuropathy in Japan

Abstract: This study confirmed differences in clinical and geographic features between early- and late-onset FAP TTR Met30. Late-onset cases may be more prevalent and widespread than previously believed.

Cited by 220 publications

References 27 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

Biophysical characterization and modulation of Transthyretin Ala97Ser

Clinical and genetic profiles of hereditary transthyretin amyloidosis in Taiwan

Contact Info

Product

Resources

About