Subscribe to RSS
DOI: 10.1590/0004-282X-ANP-2020-0590
Hereditary transthyretin-mediated amyloidosis with polyneuropathy: baseline anthropometric, demographic and disease characteristics of patients from a reference center
Amiloidose hereditária por transtirretina com polineuropatia: características basais antropométricas, demográficas e da doença em pacientes de um centro de referênciaABSTRACT
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy is a rare, inherited, multisystem, and often fatal disease caused by a variant in transthyretin (TTR) gene. Baseline characteristics of patients, especially anthropometric data, are scarce in the literature, and they are relevant to define effective treatment strategies. Objective: This study aimed to describe baseline demographic, anthropometric, and disease characteristics in a cohort of patients from a reference center in Brazil. Methods: Symptomatic patients not previously included in clinical trials and eligible for treatment were enrolled. Ethnicity, state of residence, age, sex, weight, height, body mass index (BMI), TTR variant, and Polyneuropathy Disability Score (PND) at diagnosis were analyzed. Results: Among the 108 patients enrolled, 58.33% were male, 60.19% were Caucasian, and 83.33% lived in the Southeast region. Mean age was 51.61 (±16.37) years, mean weight was 65.76 (±15.16) kg, mean height was 168.33 (±10.26) cm, and mean BMI was 23.11 (±4.45) kg/m2. The most prevalent variant was V30M (86.11%). Patients with PND score 0 presenting autonomic neuropathy were 14.81%. Patients with PND score I-II and III-IV were 52.78 and 32.41%, respectively. Mean weight and BMI were significantly lower in patients with sensory-motor manifestations. Conclusions: This is the largest cohort of patients in Brazil for whom anthropometric characteristics have been described. Baseline demographic, anthropometric, and disease data indicate that delay in diagnosis of hATTR amyloidosis with polyneuropathy is still a problem and that efforts must be made to expedite diagnosis and maximize opportunities for new disease-modifying treatments.
RESUMO
Antecedentes: Amiloidose hereditária por transtirretina (hATTR) com polineuropatia é uma doença rara, hereditária, multissistêmica, frequentemente fatal, causada por mutação no gene da transtirretina (TTR). Características dos pacientes ao diagnóstico, especialmente dados antropométricos, são raros na literatura, e são relevantes para definir estratégias terapêuticas eficazes. Objetivo: Este estudo objetivou descrever características demográficas, antropométricas, e da doença, numa coorte de pacientes de um centro de referência no Brasil. Métodos: Pacientes sintomáticos, não incluídos previamente em ensaios clínicos e elegíveis para tratamento foram recrutados. Etnia, estado de residência, idade, sexo, peso, altura, índice de massa corporal (IMC), mutação TTR e Polyneuropathy Disability Score (PND) ao diagnóstico foram analisados. Resultados: Foram incluídos 108 pacientes, sendo 58,33% do sexo masculino e 60,19% caucasianos. Na região sudeste residem 83,33%. A idade média foi 51,61 (±16,37) anos. O peso médio foi 65,76 (±15,16) Kg, a altura média foi 168,33 (±10,26) cm e o IMC médio foi 23,11 (±4,45) Kg/m2. A mutação mais prevalente foi V30M (86,11%). Pacientes com escore PND 0 apresentando neuropatia autonômica foram 14,81%. Pacientes PND I-II e PND III-IV totalizaram 52,78% e 32,41%, respectivamente. Peso e IMC médios foram significativamente menores em pacientes com manifestações sensitivo-motoras. Conclusões: Esta é a maior coorte de pacientes do Brasil que teve dados antropométricos descritos. Dados basais demográficos, antropométricos e das manifestações da doença indicam que o atraso no diagnóstico ainda é um problema, e esforços precisam ser feitos para acelerá-lo a fim de maximizar as oportunidades com os novos medicamentos que alteram o curso da doença.
Palavras-chave:
Amiloidose - Neuropatias Amiloides Familiares - Antropometria - Demografia - TerapêuticaAuthor’s contributions:
VCCS: conceptualization, data curation, project administration, supervision (leading role in all steps); writing of the original draft, review and editing; MAP, LD, FRA, RSRS, RCP: writing of the original draft, review and editing; MWC: conceptualization, data curation, project administration, supervision (leading role in all steps); writing of the original draft, review, and editing.
Publication History
Received: 15 January 2021
Accepted: 25 March 2021
Article published online:
30 January 2023
© 2021. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil
-
References
- 1 Sipe JD, Benson MD, Buxbaun JN, Ikeda S-I, Merlini G, Saraiva MJM. et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid 2016; 23 (04) 209-213 https://doi.org/10.1080/13506129.2016.1257986
- 2 Benson MD, Buxbaum JN, Eisenberg DS, Merlini G, Saraiva MJM, Sekijima Y. et al. Amyloid nomenclature 2018: recommendatios by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid 2018; 25 (04) 215-219 https://doi.org/10.1080/13506129.2018.1549825
- 3 Shin SC, Robinson-Papp J. Amyloid neuropathies. Mt Sinai J Med 2012; 79 (06) 733-748 https://doi/org/10.1002/msj.21352
- 4 Ando Y, Coelho T, Berk JL, Cruz MW, Ericzon B-G, Ikeda S-I. et al. Guideline of transthyretin- related hereditary amyloidosis for clinicians. Orphanet J Rare Dis 2013; 8: 31 https://doi.org/10.1186/1750-1172-8-31
- 5 Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med 2003; 349 (06) 583-596 https://doi.org/10.1056/NEJMra023144
- 6 Sekijima Y. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J Neurol Neurosurg Psychiatry 2015; 86 (09) 1036-1043 https://doi.org/10.1136/jnnp-2014-308724
- 7 Hawkins PN, Ando Y, Dispenzieri A, González-Duarte A, Adams D, Suhr OB. Evolving landscape in the management of transthyretin amyloidosis. Ann Med 2015; 47 (08) 625-638 https://doi.org/10.3109/07853890.2015.1068949
- 8 Waddington-Cruz M, Schmidt H, Botteman MF, Carter JA, Stewart M, Hopps M. et al. Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series. Orphanet J Rare Dis 2019; 14 (01) 34 https://doi.org/10.1186/s13023-019-1000-1
- 9 Rapezzi C, Quarta CC, Obici L, Perfetto F, Longhi S, Salvi F. et al. Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective. Eur Heart J 2013; 34 (07) 520-528 https://doi/org/10.1093/eurheartj/ehs123
- 10 Wixner J, Mundayat R, Karayal ON, Anan I, Karling P, Suhr OB. THAOS: gastrointestinal manifestations of transthyretin amyloidosis - common complications of a rare disease. Orphanet J Rare Dis 2014; 9: 61 https://doi.org/10.1186/1750-1172-9-61
- 11 Swiecicki PL, Zhen DB, Mauermann ML, Kyle RA, Zeldenrust SR, Gorgan M. et al. Hereditary ATTR Amyloidosis: a single-institution experience with 266 patients. Amyloid 2015; 22 (02) 123-131 https://doi.org/10.3109/13506129.2015.1019610
- 12 Sattianayagam PT, Hahn AF, Whelan CJ, Gibbs SDJ, Pinney JH, Stangou AJ. et al. Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant. Eur Heart J 2012; 33 (09) 1120-1127 https://doi.org/10.1093/eurheartj/ehr383
- 13 Gertz MA, Kyle RA, Thibodeau SN. Familial amyloidosis: a study of 52 north american-born patients examined during a 30-year period. Mayo Clin Proc 1992; 67 (05) P428-P440 https://doi.org/10.1016/s0025-6196(12)60388-7
- 14 Andrade C. A peculiar form of peripheral neuropathy; familiar atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain 1952; 75 (03) 408‐27-408‐27 https://doi.org/10.1093/brain/75.3.408
- 15 Coutinho PD, Lima JL, Barbosa AR, Forty years of experience with type I amyloid neuropathy: review of 436 cases. Glenner GG, de Freitas AF. Amyloid and amyloidosis. Amsterdam: Excerpta Medica; 1980: 88-98
- 16 Gonzalez-Duarte A. Autonomic involvement in hereditary transthyretin amyloidosis (hATTR amyloidosis). Clin Auton Res 2019; 29 (02) 245-251 https://doi.org/10.1007/s10286-018-0514-2
- 17 Adams D, Théaudin M, Cauquil C, Algalarrondo V, Slama M. FAP neuropathy and emerging treatments. Curr Neurol Neurosci Rep 2014; 14 (03) 345-345 https://doi.org/10.1007/s11910-013-0435-3
- 18 Conceição I, González-Duarte A, Obici L, Schimidt HH-J, Simoneau D, Ong M-L. et al. “Red‐flag” symptom clusters in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst 2016; 21 (01) 5-9 https://doi.org/10.1111/jns.12153
- 19 Cruz MW, Pinto MV, Pinto LF, Gervais R, Dias M, Perez C. et al. Baseline disease characteristics in Brazilian patients enrolled in Transthyretin Amyloidosis Outcome Survey (THAOS). Arq Neuropsiquiatr 2019; 77 (02) 96-100 https://doi.org/10.1590/0004-282X20180156
- 20 Adams D, Suhr OB, Hund E, Obici L, Tournev I, Campistol JM. et al. First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy. Curr Opin Neurol 2016; 29 (1 Suppl 1): S14-S26 https://doi.org/10.1097/WCO.20200590202005900289
- 21 Pinto MV, Barreira AA, Bulle AS, de Freitas MRG, França Jr MC, Gondim FAA. et al. Brazilian consensus for diagnosis, management and treatment of transthyretin familial amyloid polyneuropathy. Arq Neuropsiquiatr 2018; 76 (09) 609-621 https://doi.org/10.1590/0004-282x20180094
- 22 SMERP VISA. Registro ANVISA no 1021602420014 - Vyndaqel Internet. 2016 modified 2021 Sep 28 2020 Jun 10 Available from: https://www.smerp.com.br/anvisa/?ac=prodDetail&anvisaId=1021602420014
- 23 SMERP VISA. Registro ANVISA no 1936100010011 - Tegsedi Internet. 2018 modified 2021 Sep 28 2020 Jun 10 Available from: https://www.smerp.com.br/anvisa/?ac=prodDetail&anvisaId=157700002
- 24 SMERP VISA. Registro ANVISA no 157700002 - Onpattro Internet. 2019 modified 2021 Sep 28 2020 Jun 10 Available from: https://www.smerp.com.br/anvisa/?ac=prodDetail&anvisaId=1936100010011
- 25 Planté-Bordeneuve V. Transthyretin familial amyloid polyneuropathy: an update. J Neurol 2018; 265 (04) 976-983 https://doi.org/10.1007/s00415-017-8708-4
- 26 Bula de remédio.net. Tegsedi (Inotersena) [Product Label] [Internet]. PTC Farmaceutica do Brasil LTDA; 2019 2020 Jun 10 Available from: https://buladeremedio.net/ptc_farmaceutica_do_brasil_ltda/1/tegsedi/profissional
- 27 Alnylam Pharmaceuticals. Onpattro (Patisirana) [Product Label] [Internet]. 2020 2020 Jun 10 Available from: https://www.alnylam.com.br/sites/default/files/pdfs/ONPATTRO_Bula_profissional_saude_approvada.pdf
- 28 PFIZER. Vyndaqel (tafamidis meglumina) [Product Label] [Internet]. 2020. 2020 Jun 10 Available from: https://www.pfizer.com.br/sites/default/files/inline-files/Vyndaqel_Profissional_de_Saude_15.pdf
- 29 Planté-Bordeneuve V, Ferreira A, Lalu T, Zaros C, Lacroix C, Adams D. et al. Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP). Neurology 2007; 69 (07) 693-698 https://doi.org/10.1212/01.wnl.0000267338.45673.f4
- 30 Bittencourt PL, Couto CA, Clemente C, Farias AQ, Palaácios SA, Mies S. et al. Phenotypic expression of familial amyloid polyneuropathy in Brazil. Eur J Neurol 2005; 12 (04) 289-293 https://doi.org/10.1111/j.1468-1331.2004.00941.x
- 31 Cruz MW, Foguel D, Berensztejn AC, Pedrosa RC, Mundayat R, Ong M-L. The demographic, genetic, and clinical characteristics of Brazilian subjects enrolled in the transthyretin amyloidosis outcomes survey. Amyloid 2017; 24 (1 Suppl 1): 103-104 https://doi.org/10.1080/13506129.2017.1291423
- 32 Ebenezer GJ, Liu Y, Judge DP, Cunningham K, Truelove S, Carter ND. et al. Cutaneous nerve biomarkers in transthyretin familial amyloid polyneuropathy. Ann Neurol 2017; 82 (01) 44−56-44−56 https://doi.org/10.1002/ana.24972
- 33 Chao C-C, Huang C-M, Chiang H-H, Luo K-R, Kan H-W, Yang NC-C. et al. Sudomotor innervation in transthyretin amyloid neuropathy: pathology and functional correlates. Ann Neurol 2015; 78 (02) 272-283 https://doi.org/10.1002/ana.24438
- 34 Tegsedi (inotersen) [Full prescribing information] [Internet]. 2020 Jul 3 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211172lbl.pdf
- 35 Tegsedi (inotersen) [Summary of Product Characteristics] [Internet]. 2020 Jul 3 Available from: https://www.ema.europa.eu/en/documents/product-information/tegsedi-epar-product-information_en.pdf
- 36 Onpattro (patisiran) [Full prescribing information] [Internet]. 2020 Jul 3 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210922s000lbl.pdf
- 37 Onpattro (patisiran) [Summary of Product Characteristics] [Internet]. 2020 Jul 3 Available from: https://www.ema.europa.eu/en/documents/product-information/onpattro-epar-product-information_en.pdf
- 38 Vyndaqel/Vyndamax (tafamidis meglumine/tafamidis) [Full prescribing information] [Internet]. 2020 Jul 3 Available from: https://www.fda.gov/media/126283/download
- 39 Vyndaqel (tafamidis meglumine) [Summary of Product Characteristics] [Internet]. 2020 Jul 3 Available from: https://www.ema.europa.eu/en/documents/product-information/vyndaqel-epar-product-information_en.pdf