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Review
. 2019 Feb 8;14(1):34.
doi: 10.1186/s13023-019-1000-1.

Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series

Márcia Waddington-Cruz  1   2 , Hartmut Schmidt  3 , Marc F Botteman  4 , John A Carter  5 , Michelle Stewart  6 , Markay Hopps  7 , Shari Fallet  7 , Leslie Amass  8
Affiliations
Review

Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series

Márcia Waddington-Cruz et al. Orphanet J Rare Dis. .

Abstract

We describe 542 cases of symptomatic hereditary transthyretin amyloid polyneuropathy (ATTR-PN) identified through a review of the literature published between 2005 and 2016. Approximately 18% of the cases were from countries where ATTR-PN is traditionally considered to be endemic (i.e., Portugal, Japan, and Sweden). East Asia (Japan, China, Taiwan, and South Korea) contributed a sizeable combined proportion (37.0%, n = 200) with Japan (n = 92) and China (n = 71) being the primary contributors. The most common genotypes among the 65 genotypes represented in the sample were Val30Met (47.6%), Ser77Tyr (10%), Ala97Ser (6.5%), and Phe64Leu (4.4%). Cases with genotypes other than the aforementioned four had the lowest ages at onset (mean 49.2 [standard deviation {SD} 21.0; inter-quartile range {IQR}14.7]) and diagnosis (mean 53.4 [SD 21.0; IQR 14.7]). Conversely, Phe64Leu mean age of onset was 67.5 (SD 8.8; IQR 5.2) and mean age of diagnosis was 71.3 (SD 8.8; IQR 5.4). The prevalence of upper and lower limb involvement at the time of diagnosis (67 and 41%) observed across all cases is consistent with the typical presentation of ATTR-PN. Other notable findings at the time of diagnosis included a high rate of impotence among the Ala97Ser cases versus all others (67% vs. 21%) and a high rate of non-motor visual symptoms (i.e., visual opacities and glaucoma) in the Ser77Tyr cases versus all others (93% vs. 16%). Though comparisons were made descriptively and were hindered by inconsistency of reporting across the cases, these findings support the notion that ATTR-PN is a more phenotypically and geographically variable disease than is typically considered.

Keywords: Case series; Peripheral neuropathy; Rare disease; Transthyretin amyloidosis.

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Conflict of interest statement

Authors’ information

MWC is Chief of the Neuromuscular Diseases Unit at the University Hospital, Federal University of Rio, Brazil; and has been overseeing the Familial Amyloid Polyneuropathy patient care clinic (CEPARM) at the hospital for over 20 years. MWC also serves as the chair of the Transthyretin Amyloidosis Outcomes Survey (THAOS).

Ethics approval and consent to participate

Not Applicable.

Consent for publication

Not Applicable.

Competing interests

MS, MH, and LA are employees of Pfizer Inc. SF was an employee of Pfizer Inc. at the time this research was conducted. MFB is an employee of Pharmerit International, which received funding from Pfizer Inc. for study design, execution, analysis, and manuscript development. ASC was an employee of Pharmerit International at the time this research was conducted. JAC is an independent scientific consultant funded by Pharmerit International. HS and MWC were investigators for the study and were not financially compensated for collaborative efforts on publication-related activities. HS received support from FoldRx Pharmaceuticals, which was acquired by Pfizer Inc. in October 2010, as a clinical investigator. MWC received support from FoldRx Pharmaceuticals, which was acquired by Pfizer Inc. in October 2010, as a clinical investigator; has served on the scientific advisory board of Pfizer Inc.; received funding from Pfizer Inc. for scientific meeting expenses (travel, accommodations, and registration); and received research support from the National Institutes of Health. She currently serves on the THAOS (natural history disease registry) scientific advisory board.

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Figures

Fig. 1
Fig. 1
This figure depicts the taxonomy of ATTR-PN symptoms extracted for analysis CTS is carpal tunnel syndrome
See this image and copyright information in PMC

References

    1. Waddington-Cruz M, Schmidt H, Botteman MF, et al. International Society of Amyloidosis - XV International Symposium on Amyloidosis (ISA) 2016. Epidemiological and clinical characteristics of persons with transthyretin familial amyloid polyneuropathy: A global synthesis of 532 cases.
    1. Plante-Bordeneuve V. Update in the diagnosis and management of transthyretin familial amyloid polyneuropathy. J Neurol. 2014;261(6):1227–1233. doi: 10.1007/s00415-014-7373-0. - DOI - PubMed
    1. Misu KI, Hattori N, Nagamatsu M, et al. Late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy) unrelated to endemic focus in Japan. Clinicopathological and genetic features. Brain. 1999;122(1):1951–1962. doi: 10.1093/brain/122.10.1951. - DOI - PubMed
    1. Schmidt HH, Waddington-Cruz M, Botteman MF, et al. Estimating the global prevalence of transthyretin familial amyloid polyneuropathy. Muscle Nerve. 2018;57(5):829–837. doi: 10.1002/mus.26034. - DOI - PMC - PubMed
    1. Yamashita T, Ando Y, Okamoto S, et al. Long-term survival after liver transplantation in patients with familial amyloid polyneuropathy. Neurology. 2012;78(9):637–643. doi: 10.1212/WNL.0b013e318248df18. - DOI - PubMed

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