Variant transthyretin amyloidosis (ATTRv) polyneuropathy in Greece: a broad overview with a focus on non-endemic unexplored regions of the country

Kastritis, Efstathios; Kontogeorgiou, Zoi; Kartanou, Chrisoula; Kokotis, Panagiotis; Rentzos, Michael; Breza, Marianthi; Kleopa, Kleopas A.; Christodoulou, Kyproula; Oikonomou, Evangelos; Anastasakis, Aris; Angelidakis, Panagiotis; Sarmas, Ioannis; Kargiotis, Odysseas; Tzagournissakis, Minas; Zaganas, Ioannis; Foukarakis, Emmanouil; Sachpekidis, Vasileios; Papathoma, Alexandra; Πάνας, Μάριος; Stefanis, Leonidas; Karadima, Georgia

doi:10.1016/j.nmd.2021.09.008

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…13 , 14 Concerning Greece however, except for the occasional description of families with the p.Val50Met variant, 12 , 21 there are no systematic studies on the prevalence of hATTR, although it has been extrapolated to be 3–79 per million 9 and recently estimated to be below 1/100,000. 15 Our study systemically evaluated the prevalence of hATTR in a defined area of Greece, thereby establishing that Crete is an endemic area for this disorder.…”

Section: Discussionmentioning

confidence: 99%

“…14 Only a recent study has evaluated the clinical phenotypes, the variety of causative TTR gene variants and the prevalence of hATTR; however, this study focused in areas of Greece other than Crete. 15 Our cohort study, spanning a 27-year period, was designed to identify and follow all cases of hATTR that occur in Crete with the goal of evaluating their epidemiologic, clinical, and genetic features and treatment approaches. The results revealed that hATTR in Crete is relatively frequent and characterized by genetic and clinical heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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High Hereditary Transthyretin-Related Amyloidosis Prevalence in Crete

et al. 2022

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Background and ObjectivesOur goal was to study hereditary transthyretin-related amyloidosis (hATTR) in Crete, Greece.MethodsWe aimed at ascertaining all hATTR cases in Crete, an island of 0.62 million people. For this, we evaluated patients with polyneuropathy, autonomic involvement, cardiomyopathy, and/or ophthalmopathy suggestive of hATTR, who presented to the physicians of this study or were referred to them by other physicians. Genetic analyses were performed on all patients suspected of suffering from hATTR. We included in our observational longitudinal cohort study all individuals, residents of Crete, who, during the study period (1993–2019), were found to carry a pathogenic TTR variant.ResultsOver the past 27 years, 30 individuals (15 female patients, 15 male patients), from 12 apparently unrelated families, were diagnosed with hATTR, whereas evaluation of their offspring identified 5 asymptomatic TTR pathogenic variant carriers. The most prevalent TTR variant detected was p.Val50Met, affecting 19 patients (11 female patients, 8 male patients) and causing a rather consistent phenotype characterized by predominant polyneuropathy of early adult onset (median age of symptom onset: 30 years; range: 18–37 years). Specifically, patients affected by the p.Val50Met TTR variant experienced progressive sensorimotor disturbances, involving mainly the lower extremities, associated with autonomic and/or gastrointestinal dysfunction. The second most frequent TTR variant was p.Val114Ala, found in 10 patients (4 female patients, 6 male patients) who were affected at an older age (median age of symptom onset: 70 years; range: 54–78 years). This variant caused a predominantly cardiomyopathic phenotype, manifested by congestive heart failure and associated with peripheral neuropathy, carpal tunnel syndrome, and/or autonomic involvement. In these patients, cardiac amyloid deposition was detected on 99m-technetium pyrophosphate scintigraphy and/or heart biopsy. The third TTR variant (p.Arg54Gly) was found in a 50-year-old male patient with ophthalmopathy due to vitreous opacities and positive family history for visual loss. As 22 patients were alive at the end of the study, we calculated the hATTR prevalence in Crete to be 35 cases per 1 million inhabitants.DiscussionOur study revealed that the prevalence of hATTR in Crete is one of the world's highest. Three different pathogenic TTR variants causing distinct clinical phenotypes were identified in this relatively small population pool.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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High Hereditary Transthyretin-Related Amyloidosis Prevalence in Crete

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Transthyretin amyloidosis cardiomyopathy in Greece: Clinical insights from the National Referral Center

Bampatsias,

Theodorakakou,

Briasoulis

et al. 2023

Hellenic Journal of Cardiology

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Optimal practices for the management of hereditary transthyretin amyloidosis: real-world experience from Japan, Brazil, and Portugal

Ando,

Waddington-Cruz,

Sekijima

et al. 2023

Orphanet J Rare Dis

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Hereditary transthyretin (ATTRv) amyloidosis is a rare and autosomal dominant disorder associated with mutations in the transthyretin gene. Patients present with diverse symptoms related to sensory, motor, and autonomic neuropathy, as well as gastrointestinal, ocular, cardiac, renal and orthopedic symptoms, resulting from the deposition of transthyretin amyloid fibrils in multiple organs. The progressive nature of ATTRv amyloidosis necessitates pre- and post-onset monitoring of the disease. This review article is primarily based on a collation of discussions from a medical advisory board meeting in August 2021. In this article, we summarize the best practices in amyloidosis centers in three major endemic countries for ATTRv amyloidosis (Japan, Brazil, and Portugal), where most patients carry the Val30Met mutation in the transthyretin gene and the patients’ genetic background was proven to be the same. The discussions highlighted the similarities and differences in the management of asymptomatic gene mutation carriers among the three countries in terms of the use of noninvasive tests and tissue biopsies and timing of starting the investigations. In addition, this article discusses a set of practical tests and examinations for monitoring disease progression applicable to neurologists working in diverse medical settings and generalizable in non-endemic countries and areas. This set of assessments consists of periodic (every 6 to 12 months) evaluations of patients’ nutritional status and autonomic, renal, cardiac, ophthalmologic, and neurological functions. Physical examinations and patient-reported outcome assessments should be also scheduled every 6 to 12 months. Programs for monitoring gene mutation carriers and robust referral networks can aid in appropriate patient management in pre- to post-onset stages. For pre- and post-symptom onset testing for ATTRv amyloidosis, various noninvasive techniques are available; however, their applicability differs depending on the medical setting in each country and region, and the optimal option should be selected in view of the clinical settings, medical environment, and available healthcare resources in each region.

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Variant transthyretin amyloidosis (ATTRv) polyneuropathy in Greece: a broad overview with a focus on non-endemic unexplored regions of the country

Cited by 3 publications

References 27 publications

High Hereditary Transthyretin-Related Amyloidosis Prevalence in Crete

High Hereditary Transthyretin-Related Amyloidosis Prevalence in Crete

Transthyretin amyloidosis cardiomyopathy in Greece: Clinical insights from the National Referral Center

Optimal practices for the management of hereditary transthyretin amyloidosis: real-world experience from Japan, Brazil, and Portugal

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