Ala97Ser mutation is common among ethnic Chinese Malaysians with transthyretin familial amyloid polyneuropathy

Low, Soon-Chai; Tan, Cheng Yin; Sari, Nor Ashikin Md; Ahmad‐Annuar, Azlina; Wong, Kum Thong; Lin, Kon‐Ping; Shahrizaila, Nortina; Tan, Chong Tin; Goh, Khean Jin

doi:10.1080/13506129.2019.1582479

Cited by 13 publications

(11 citation statements)

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“…Anticipation (younger onset in the offspring, usually with increased severity) has also been repeatedly reported in ATTRV30M but is not common in ATTRA97S [18,[27][28][29][30][31]. Similar to patients from Malaysia [21], the paternal or maternal ancestors of our patients migrated from southern China in the 19th century. It is possible that ATTRA97S-PN patients residing in Southeast Asian countries share a similar ancestor with Han-Taiwanese/Han-Chinese patients.…”

Section: Discussionsupporting

confidence: 73%

“…It is also a common TTR mutation in mainland China (Han-Chinese), particularly in southern China [17][18][19][20]. One study from Malaysia reported ATTRA97S-PN in nine Chinese Malaysian patients [21]. In fact, this mutation has never been reported in other populations so far.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, symptomatic patients were not restricted to late adulthood and elderly individuals. Patients' symptoms may start in their early 30 s. A review of the English literature in the PubMed search engine revealed 12 clinical studies with clinical data (including case reports) of ATTRA97S-PN [6][7][8][9][10][17][18][19][20][21][22][23]. The first case was reported in 1999 [23].…”

Section: Discussionmentioning

confidence: 99%

“…The first case was reported in 1999 [23]. Additional file 2 shows the epidemiologic data and clinical features of Thai patients in comparison to those in 12 previous reports [6][7][8][9][10][17][18][19][20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

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Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

et al. 2021

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Background Ala97Ser transthyretin amyloidosis-associated polyneuropathy (ATTRA97S-PN) is a rare form of inherited polyneuropathy, usually manifesting with late-onset (> 50) progressive polyneuropathy. This mutation is mostly prevalent in Taiwanese and Han-Chinese individuals. The aim of this study was to describe the clinical and comprehensive neurophysiological profiles of ATTRA97S-PN in Thai patients. Methods The clinical profiles and serial neurophysiologic studies (nerve conduction study (NCS), quantitative sensory test (QST), and comprehensive autonomic function test (AFT)) of symptomatic ATTRA97S-PN patients who had been followed-up at King Chulalongkorn Memorial Hospital during 2010–2020 were retrospectively reviewed. Results Nine symptomatic patients (55.6 % were male) from four unrelated families were included. All were Thais of mixed Thai Chinese descent. The mean age of onset was 48.3 (32–60) years. The mean age at diagnosis was 54.8 (33–66) years. Three patients developed early-onset (< 40y) polyneuropathy. The mean Neuropathy Impairment Score was 41.33 (10–92) at diagnosis. Sensory (9/9) and autonomic (9/9) neuropathies were more frequent than motor neuropathy (5/9), which appeared in the late stage of disease. Hypoesthesia in the feet, and gastrointestinal autonomic symptoms were frequently reported as the initial symptoms. The course of neuropathy progressed over years to decades. The worsening of neuropathy tended to progress faster once motor nerves were affected in both clinical and neurophysiological aspects. Concurrent cardiac amyloidosis was found in 6/9 patients. NCS showed length-dependent sensorimotor axonal polyneuropathy in 5/9 patients, and median neuropathy at the wrist (mostly bilateral) in 7/9 patients. QST showed abnormalities in the vibratory detection threshold, the cold detection threshold and the heat pain sensation in 8/9, 8/9 and 7/7 tested patients, respectively. AFT results were abnormal in all. The mean composite autonomic severity score was 5 (3–9). Conclusions This clinical study is the first of ATTRA97S-PN in Thai patients. The mixed polyneuropathy-cardiopathy phenotype was the most common manifestation. In this cohort, the age of onset was lower, and the course of neuropathy was relatively longer, than that in previous studies. Some patients may develop early-onset polyneuropathy. This mutation has not yet been documented in any population other than Han Chinese-related populations, probably suggesting a founder effect. Further studies are warranted.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

et al. 2021

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“…Various mutations of hereditary transthyretin amyloidosis (ATTRv) or familial amyloid polyneuropathy (FAP), which affects motor, sensory, and autonomic nerves, encompass different phenotypes (Ando et al, 2013;Carr et al, 2016;Sridharan et al, 2018;Adams et al, 2019;Damy et al, 2019;Dang et al, 2019;Lane et al, 2019). While the V30M (p.V50M) (Benson et al, 2020) with polyneuropathy is the most common pathogenic variant in Japan and around the world (Ikeda et al, 2002;Adams et al, 2015;Coelho et al, 2018;Yamashita et al, 2019), A97S (p.A117S) (Benson et al, 2020) constitutes the most frequent mutation in Taiwan and has been reported in China (Du et al, 2021), Malaysia (Low et al, 2019), and Thailand (Pasutharnchat et al, 2021). V30M in Japan had two onset patterns, namely, early-vs. late-onset type (Koike et al, 2002(Koike et al, , 2004(Koike et al, , 2012, and the latter was also reported in Portugal and France (Conceição and De Carvalho, 2007;Dohrn et al, 2013;Buades-Reinés et al, 2016;Pinto et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Unique Phenotypes With Corresponding Pathology in Late-Onset Hereditary Transthyretin Amyloidosis of A97S vs. V30M

Hsueh

Chao

Chang

et al. 2022

Front. Aging Neurosci.

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ObjectiveHereditary transthyretin amyloidosis (ATTRv) encompasses different phenotypes among various genotypes. The analysis of the natural history and risk factors of faster progression in different genotypes would refine the treatment strategy.MethodsThe clinical manifestations of ATTRv from A97S (p.A117S) of Taiwanese and late-onset V30M (p.V50M) of Japanese were compared. An autopsy study of A97S was performed.ResultsThere existed three unique features in the A97S cohort compared to the V30M cohort: (1) dysphagia, (2) carpal tunnel syndrome (CTS), and (3) onset age. First, dysphagia was common in A97S (53.4%) but not in V30M and served as a contributor to fast disease progression. All phases of swallowing were affected. In the autopsy pathology, there were extensive amyloid deposits in the viscera and nerves of the tongue, larynx, and esophagus. In A97S, 45 patients (43.3%) had a history of CTS before the onset of length-dependent symptoms by 3 years. The amyloid deposition was more prominent in the median nerve than that in the transverse carpal ligament. The onset age at different stages was younger in the A97S cohort than the V30M cohort by 4–5 years.ConclusionThese phenotypic characteristics together with autopsy pathology in A97S are distinct from V30M. Early dysphagia in A97S correlated with fast progression. In A97S, median neuropathy leading to CTS might be in a continuous spectrum of ATTRv course rather than an independent disease entity. Such observations may serve as a foundation to explore and analyze unique phenotypes among various genotypes.

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Cardiomyopathy correlates to nerve damage in p.A117Slate‐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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Ala97Ser mutation is common among ethnic Chinese Malaysians with transthyretin familial amyloid polyneuropathy

Cited by 13 publications

References 3 publications

Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

Unique Phenotypes With Corresponding Pathology in Late-Onset Hereditary Transthyretin Amyloidosis of A97S vs. V30M

Cardiomyopathy correlates to nerve damage in p.A117Slate‐onset transthyretin amyloid polyneuropathy

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