Hereditary Transthyretin Amyloidosis Polyneuropathy

Abstract

In the last decade, we have witnessed dramatic improvements in the diagnosis, workup, management, and monitoring of patients with hereditary transthyretin amyloidosis (ATTRv). Updated imaging techniques (e.g., ^99mTc-PYP scan) are increasingly being used in place of tissue biopsies for confirmation of disease. Novel treatments now include antisense oligonucleotide and RNA interference drugs, whereas new applications such as CRISPR and amyloid antibodies are being studied for potential use in the future. These treatments have dramatically improved quality of life and increased survival in patients with ATTRv. Despite these breakthroughs, many challenges remain. Some of these challenges include early recognition and diagnosis of ATTRv, monitoring and initiation of treatment in asymptomatic or paucisymptomatic carriers, adequate treatment in people with mixed phenotype (i.e., cardiac and neurological), and the emergence of new phenotypes in people living longer with the disease (i.e., central nervous system and ocular complications). Research in those areas of deficit is ongoing, and in the future, we may have preventive therapies, better biomarkers, more efficient therapies for organs that we cannot currently target, and enhanced diagnostic techniques with the help of novel imaging techniques and artificial intelligence. In this review, we will summarize the current knowledge about polyneuropathy related to ATTRv and its management, discuss methods to improve early diagnosis and monitoring, and discuss emerging trends.

Keywords

ATTRv amyloidosis - familial amyloid polyneuropathy - cardiac amyloidosis - hereditary transthyretin amyloidosis

Publikationsverlauf

Artikel online veröffentlicht:
15. Oktober 2024

• References

• 1 Maurer MS, Schwartz JH, Gundapaneni B. et al; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 2018; 379 (11) 1007-1016
• 2 Kanda Y, Goodman DS, Canfield RE, Morgan FJ. The amino acid sequence of human plasma prealbumin. J Biol Chem 1974; 249 (21) 6796-6805
• 3 Kelly JW, Colon W, Lai Z. et al. Transthyretin quaternary and tertiary structural changes facilitate misassembly into amyloid. Adv Protein Chem 1997; 50: 161-181
• 4 Nativi-Nicolau JN, Karam C, Khella S, Maurer MS. Screening for ATTR amyloidosis in the clinic: overlapping disorders, misdiagnosis, and multiorgan awareness. Heart Fail Rev 2022; 27 (03) 785-793
• 5 Karam C, Dimitrova D, Christ M, Heitner SB. Carpal tunnel syndrome and associated symptoms as first manifestation of hATTR amyloidosis. Neurol Clin Pract 2019; 9 (04) 309-313
• 6 Andrade C. A peculiar form of peripheral neuropathy; familiar atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain 1952; 75 (03) 408-427
• 7 Benson MD, Waddington-Cruz M, Berk JL. et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. N Engl J Med 2018; 379 (01) 22-31
• 8 Adams D, Gonzalez-Duarte A, O'Riordan WD. et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med 2018; 379 (01) 11-21
• 9 Berk JL, Suhr OB, Obici L. et al; Diflunisal Trial Consortium. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA 2013; 310 (24) 2658-2667
• 10 Coelho T, Maia LF, Martins da Silva A. et al. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology 2012; 79 (08) 785-792
• 11 Schmidt HH, Waddington-Cruz M, Botteman MF. et al. Estimating the global prevalence of transthyretin familial amyloid polyneuropathy. Muscle Nerve 2018; 57 (05) 829-837
• 12 Schmidt H, Cruz MW, Botteman MF. et al. Global epidemiology of transthyretin hereditary amyloid polyneuropathy: a systematic review. Amyloid 2017; 24 (sup1): 111-112
• 13 Carroll A, Dyck PJ, de Carvalho M. et al. Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis. J Neurol Neurosurg Psychiatry 2022; 93 (06) 668-678
• 14 Conceição I. Clinical features of TTR-FAP in Portugal. Amyloid 2012; 19 (Suppl. 01) 71-72
• 15 Planté-Bordeneuve V, Carayol J, Ferreira A. et al. Genetic study of transthyretin amyloid neuropathies: carrier risks among French and Portuguese families. J Med Genet 2003; 40 (11) e120
• 16 Hellman U, Alarcon F, Lundgren HE, Suhr OB, Bonaiti-Pellié C, Planté-Bordeneuve V. Heterogeneity of penetrance in familial amyloid polyneuropathy, ATTR Val30Met, in the Swedish population. Amyloid 2008; 15 (03) 181-186
• 17 Jacobson DR, Pastore RD, Yaghoubian R. et al. Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans. N Engl J Med 1997; 336 (07) 466-473
• 18 Obi CA, Mostertz WC, Griffin JM, Judge DP. ATTR epidemiology, genetics, and prognostic factors. Methodist DeBakey Cardiovasc J 2022; 18 (02) 17-26
• 19 Madhani A, Sabogal N, Massillon D. et al. Clinical penetrance of the transthyretin V122I variant in older Black patients with heart failure: the SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study. J Am Heart Assoc 2023; 12 (15) e028973
• 20 Saporta MAC, Zaros C, Cruz MW. et al. Penetrance estimation of TTR familial amyloid polyneuropathy (type I) in Brazilian families. Eur J Neurol 2009; 16 (03) 337-341
• 21 Poli L, Labella B, Cotti Piccinelli S. et al. Hereditary transthyretin amyloidosis: a comprehensive review with a focus on peripheral neuropathy. Front Neurol 2023; 14: 1242815
• 22 Lin X, Yarlas A, Vera-Llonch M. et al. Rate of neuropathic progression in hereditary transthyretin amyloidosis with polyneuropathy and other peripheral neuropathies: a systematic review and meta-analysis. BMC Neurol 2021; 21 (01) 70
• 23 Wang S, Peng W, Pang M. et al. Clinical profile and prognosis of hereditary transthyretin amyloid cardiomyopathy: a single-center study in South China. Front Cardiovasc Med 2022; 9: 900313
• 24 Antonopoulos AS, Panagiotopoulos I, Kouroutzoglou A. et al. Prevalence and clinical outcomes of transthyretin amyloidosis: a systematic review and meta-analysis. Eur J Heart Fail 2022; 24 (09) 1677-1696
• 25 Gonzalez-Duarte A, Valdés-Ferrer SI, Cantú-Brito C. Characteristics and natural history of autonomic involvement in hereditary ATTR amyloidosis: a systematic review. Clin Auton Res 2019; 29 (Suppl. 01) 1-9
• 26 Blake CCF, Geisow MJ, Swan IDA, Rerat C, Rerat B. Structure of human plasma prealbumin at 2-5 A resolution. A preliminary report on the polypeptide chain conformation, quaternary structure and thyroxine binding. J Mol Biol 1974; 88 (01) 1-12
• 27 Saraiva MJM. Transthyretin mutations in hyperthyroxinemia and amyloid diseases. Hum Mutat 2001; 17 (06) 493-503
• 28 Dickson PW, Aldred AR, Marley PD, Tu GF, Howlett GJ, Schreiber G. High prealbumin and transferrin mRNA levels in the choroid plexus of rat brain. Biochem Biophys Res Commun 1985; 127 (03) 890-895
• 29 Soprano DR, Herbert J, Soprano KJ, Schon EA, Goodman DS. Demonstration of transthyretin mRNA in the brain and other extrahepatic tissues in the rat. J Biol Chem 1985; 260 (21) 11793-11798
• 30 Guimaraes A, Viana Pinherio A, Leite I. Sural nerve biopsy in familial amyloidotic polyneuropathy: a morphological and morphometric polyneuropathy. In: Natvig JB, Forre O, Husby G. et al., eds. Amyloid and Amyloidosis. Kluwer Academic Publishers; 1990: 493-498
• 31 Lobato L, Rocha A. Transthyretin amyloidosis and the kidney. Clin J Am Soc Nephrol 2012; 7 (08) 1337-1346
• 32 Lobato L, Beirão I, Guimarães SM. et al. Familial amyloid polyneuropathy type I (Portuguese): distribution and characterization of renal amyloid deposits. Am J Kidney Dis 1998; 31 (06) 940-946
• 33 Wixner J, Törnblom H, Karling P, Anan I, Lindberg G. Abnormal small bowel motility in patients with hereditary transthyretin amyloidosis. Neurogastroenterol Motil 2018; 30 (09) e13354
• 34 Ikeda SI, Makishita H, Oguchi K, Yanagisawa N, Nagata T. Gastrointestinal amyloid deposition in familial amyloid polyneuropathy. Neurology 1982; 32 (12) 1364-1368
• 35 Obayashi K, Olsson M, Anan I. et al. Impact of serotonin transporter and catechol-O-methyl transferase genes polymorphism on gastrointestinal dysfunction in Swedish and Japanese familial amyloidotic polyneuropathy patients. Clin Chim Acta 2008; 398 (1–2): 10-14
• 36 El-Salhy M, Suhr O. Endocrine cells in rectal biopsy specimens from patients with familial amyloidotic polyneuropathy. Scand J Gastroenterol 1996; 31 (01) 68-73
• 37 Anan I, El-Salhy M, Ando Y. et al. Colonic endocrine cells in patients with familial amyloidotic polyneuropathy. J Intern Med 1999; 245 (05) 469-473
• 38 Hou X, Parkington HC, Coleman HA. et al. Transthyretin oligomers induce calcium influx via voltage-gated calcium channels. J Neurochem 2007; 100 (02) 446-457
• 39 Said G. Familial amyloid polyneuropathy: mechanisms leading to nerve degeneration. Amyloid 2003; 10 (Suppl. 01) 7-12
• 40 Koike H, Ikeda S, Takahashi M. et al. Schwann cell and endothelial cell damage in transthyretin familial amyloid polyneuropathy. Neurology 2016; 87 (21) 2220-2229
• 41 Kollmer J, Hund E, Hornung B. et al. In vivo detection of nerve injury in familial amyloid polyneuropathy by magnetic resonance neurography. Brain 2015; 138 (Pt 3): 549-562
• 42 Ihse E, Ybo A, Suhr O, Lindqvist P, Backman C, Westermark P. Amyloid fibril composition is related to the phenotype of hereditary transthyretin V30M amyloidosis. J Pathol 2008; 216 (02) 253-261
• 43 Koike H, Ando Y, Ueda M. et al. Distinct characteristics of amyloid deposits in early- and late-onset transthyretin Val30Met familial amyloid polyneuropathy. J Neurol Sci 2009; 287 (1-2): 178-184
• 44 Koike H, Misu K, Sugiura M. et al. Pathology of early- vs late-onset TTR Met30 familial amyloid polyneuropathy. Neurology 2004; 63 (01) 129-138
• 45 Sobue G, Nakao N, Murakami K. et al. Type I familial amyloid polyneuropathy. A pathological study of the peripheral nervous system. Brain 1990; 113 (Pt 4): 903-919
• 46 Wakita Y, Sato T, Chosa K. et al. Characterization of non-amyloidogenic G101S transthyretin. Biol Pharm Bull 2018; 41 (04) 628-636
• 47 Miller M, Pal A, Albusairi W. et al. Enthalpy-driven stabilization of transthyretin by AG10 mimics a naturally occurring genetic variant that protects from transthyretin amyloidosis. J Med Chem 2018; 61 (17) 7862-7876
• 48 Sant'Anna R, Almeida MR, Varejāo N. et al. Cavity filling mutations at the thyroxine-binding site dramatically increase transthyretin stability and prevent its aggregation. Sci Rep 2017; 7: 44709
• 49 Lim A, Prokaeva T, Connor LH, Falk RH, Skinner M, Costello CE. Identification of a novel transthyretin Thr59Lys/Arg104His. A case of compound heterozygosity in a Chinese patient diagnosed with familial transthyretin amyloidosis. Amyloid 2002; 9 (02) 134-140
• 50 Hornstrup LS, Frikke-Schmidt R, Nordestgaard BG, Tybjærg-Hansen A. Genetic stabilization of transthyretin, cerebrovascular disease, and life expectancy. Arterioscler Thromb Vasc Biol 2013; 33 (06) 1441-1447
• 51 Dispenzieri A, Coelho T, Conceição I. et al; THAOS investigators. Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update. Orphanet J Rare Dis 2022; 17 (01) 236
• 52 Kaku M, Berk JL. Neuropathy associated with systemic amyloidosis. Semin Neurol 2019; 39 (05) 578-588
• 53 Gertz MA, Benson MD, Dyck PJ. et al. Diagnosis, prognosis, and therapy of transthyretin amyloidosis. J Am Coll Cardiol 2015; 66 (21) 2451-2466
• 54 Koike H, Misu K, Ikeda S. et al; Study Group for Hereditary Neuropathy in Japan. Type I (transthyretin Met30) familial amyloid polyneuropathy in Japan: early- vs late-onset form. Arch Neurol 2002; 59 (11) 1771-1776
• 55 Pinto MV, Pinto LF, Dias M. et al. Late-onset hereditary ATTR V30M amyloidosis with polyneuropathy: characterization of Brazilian subjects from the THAOS registry. J Neurol Sci 2019; 403: 1-6
• 56 Sattianayagam PT, Hahn AF, Whelan CJ. 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
• 57 Kaku MC, Bhadola S, Berk JL, Sanchorawala V, Connors LH, Lau KHV. Neurological manifestations of hereditary transthyretin amyloidosis: a focus on diagnostic delays. Amyloid 2022; 29 (03) 184-189
• 58 da Silva-Batista JA, Marques Jr W, Oliveira MTJS. et al. Presence of val30Met and val122ile mutations in a patient with hereditary amyloidosis. J Hum Genet 2020; 65 (08) 711-713
• 59 Prokaeva T, Klimtchuk ES, Feschenko P. et al. An additive destabilising effect of compound T60I and V122I substitutions in ATTRv amyloidosis. Amyloid 2023; 30 (02) 141-152
• 60 Taipa R, Sousa L, Pinto M. et al. Neuropathology of central nervous system involvement in TTR amyloidosis. Acta Neuropathol 2023; 145 (01) 113-126
• 61 Maia LF, Magalhães R, Freitas J. et al. CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings. J Neurol Neurosurg Psychiatry 2015; 86 (02) 159-167
• 62 Karam C, Dimitrova D, Heitner SB. Misdiagnosis of hATTR amyloidosis: a single US site experience. Amyloid 2020; 27 (01) 69-70
• 63 Vera-Llonch M, Reddy SR, Chang E, Tarbox MH, Pollock M. The patient journey toward a diagnosis of hereditary transthyretin (ATTRv) amyloidosis. Orphanet J Rare Dis 2021; 16 (01) 25
• 64 Benson MD, Dasgupta NR, Rao R. Diagnosis and screening of patients with hereditary transthyretin amyloidosis (Hattr): current strategies and guidelines. Ther Clin Risk Manag 2020; 16: 749-758
• 65 Karam C, Mauermann ML, Gonzalez-Duarte A. et al. Diagnosis and treatment of hereditary transthyretin amyloidosis with polyneuropathy in the United States: recommendations from a panel of experts. Muscle Nerve 2024; 69 (03) 273-287
• 66 Adams D, Tournev IL, Taylor MS. et al; HELIOS-A Collaborators. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid 2023; 30 (01) 1-9
• 67 Coelho T, Marques Jr W, Dasgupta NR. et al; NEURO-TTRansform Investigators. Eplontersen for hereditary transthyretin amyloidosis with polyneuropathy. JAMA 2023; 330 (15) 1448-1458
• 68 Ticau S, Aldinc E, Polydefkis M. et al; Patisiran Global OLE Collaborators. Treatment response and neurofilament light chain levels with long-term patisiran in hereditary transthyretin-mediated amyloidosis with polyneuropathy: 24-month results of an open-label extension study. Amyloid 2024; 31 (01) 1-11
• 69 Carroll AS, Razvi Y, O'Donnell L. et al. Serum neurofilament light chain in hereditary transthyretin amyloidosis: validation in real-life practice. Amyloid 2024; 31 (02) 95-104
• 70 Vogt B, Chahin N, Wiszniewski W, Ragole T, Karam C. Screening for genetic mutations in patients with neuropathy without definite etiology is useful. J Neurol 2020; 267 (09) 2648-2654
• 71 Sekijima Y, Nakamura K. Hereditary transthyretin amyloidosis. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A. eds. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993
• 72 Reddi HV, Jenkins S, Theis J. et al. Homozygosity for the V122I mutation in transthyretin is associated with earlier onset of cardiac amyloidosis in the African American population in the seventh decade of life. J Mol Diagn 2014; 16 (01) 68-74
• 73 Obici L, Kuks JB, Buades J. et al; European Network for TTR-FAP (ATTReuNET). Recommendations for presymptomatic genetic testing and management of individuals at risk for hereditary transthyretin amyloidosis. Curr Opin Neurol 2016; 29 (Suppl. 01) S27-S35
• 74 Lozeron P, Mariani LL, Dodet P. et al. Transthyretin amyloid polyneuropathies mimicking a demyelinating polyneuropathy. Neurology 2018; 91 (02) e143-e152
• 75 Salvalaggio A, Coraci D, Cacciavillani M. et al. Nerve ultrasound in hereditary transthyretin amyloidosis: red flags and possible progression biomarkers. J Neurol 2021; 268 (01) 189-198
• 76 Hodel J, Benadjaoud S, Benadjaoud MA, Lefaucheur JP, Planté-Bordeneuve V. 3-T MR neurography of lumbo-sacral plexus in hereditary transthyretin-related amyloidosis with polyneuropathy. Eur Radiol 2022; 32 (11) 7865-7871
• 77 Gasparotti R, Salvalaggio A, Corbo D. et al. Magnetic resonance neurography and diffusion tensor imaging of the sciatic nerve in hereditary transthyretin amyloidosis polyneuropathy. J Neurol 2023; 270 (10) 4827-4840
• 78 Ebenezer GJ, Liu Y, Judge DP. et al. Cutaneous nerve biomarkers in transthyretin familial amyloid polyneuropathy. Ann Neurol 2017; 82 (01) 44-56
• 79 Luigetti M, Romozzi M, Bisogni G. et al. hATTR pathology: nerve biopsy results from Italian referral centers. Brain Sci 2020; 10 (11) 780
• 80 Samões R, Taipa R, Valdrez K. et al. Amyloid detection in the transverse carpal ligament of patients with hereditary ATTR V30M amyloidosis and carpal tunnel syndrome. Amyloid 2017; 24 (02) 73-77
• 81 de Paula Eduardo F, de Mello Bezinelli L, de Carvalho DLC. et al. Minor salivary gland biopsy for the diagnosis of familial amyloid polyneuropathy. Neurol Sci 2017; 38 (02) 311-318
• 82 Quarta CC, Gonzalez-Lopez E, Gilbertson JA. et al. Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis. Eur Heart J 2017; 38 (24) 1905-1908
• 83 Paulsson Rokke H, Sadat Gousheh N, Westermark P. et al. Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspected transthyretin amyloidosis. Orphanet J Rare Dis 2020; 15 (01) 278
• 84 Gillmore JD, Maurer MS, Falk RH. et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation 2016; 133 (24) 2404-2412
• 85 Chatzantonis G, Bietenbeck M, Elsanhoury A. et al. Diagnostic value of cardiovascular magnetic resonance in comparison to endomyocardial biopsy in cardiac amyloidosis: a multi-centre study. Clin Res Cardiol 2021; 110 (04) 555-568
• 86 Gilbertson JA, Theis JD, Vrana JA. et al. A comparison of immunohistochemistry and mass spectrometry for determining the amyloid fibril protein from formalin-fixed biopsy tissue. J Clin Pathol 2015; 68 (04) 314-317
• 87 Klein CJ, Vrana JA, Theis JD. et al. Mass spectrometric-based proteomic analysis of amyloid neuropathy type in nerve tissue. Arch Neurol 2011; 68 (02) 195-199
• 88 Castano A, Haq M, Narotsky DL. et al. Multicenter study of planar technetium 99m pyrophosphate cardiac imaging: predicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol 2016; 1 (08) 880-889
• 89 Dyck PJB, González-Duarte A, Obici L. et al. Development of measures of polyneuropathy impairment in hATTR amyloidosis: from NIS to mNIS + 7. J Neurol Sci 2019; 405: 116424
• 90 Adams D, Samuel D, Goulon-Goeau C. et al. The course and prognostic factors of familial amyloid polyneuropathy after liver transplantation. Brain 2000; 123 (Pt 7): 1495-1504
• 91 Yamashita T, Ando Y, Okamoto S. et al. Long-term survival after liver transplantation in patients with familial amyloid polyneuropathy. Neurology 2012; 78 (09) 637-643
• 92 Carvalho A, Rocha A, Lobato L. Liver transplantation in transthyretin amyloidosis: issues and challenges. Liver Transpl 2015; 21 (03) 282-292
• 93 Maurer MS, Kale P, Fontana M. et al; APOLLO-B Trial Investigators. Patisiran treatment in patients with transthyretin cardiac amyloidosis. N Engl J Med 2023; 389 (17) 1553-1565
• 94 Dasgupta NR, Rissing SM, Smith J, Jung J, Benson MD. Inotersen therapy of transthyretin amyloid cardiomyopathy. Amyloid 2020; 27 (01) 52-58
• 95 Coelho T, Adams D, Conceição I. et al. A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. Orphanet J Rare Dis 2020; 15 (01) 179
• 96 Qarni TN, Jones FJS, Drachman B. et al. Treatment characteristics of patients with hereditary transthyretin amyloidosis: a cohort study. Orphanet J Rare Dis 2024; 19 (01) 191
• 97 Gillmore JD, Judge DP, Cappelli F. et al; ATTRibute-CM Investigators. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. N Engl J Med 2024; 390 (02) 132-142
• 98 Gamez J, Salvadó M, Reig N. et al. Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study. Amyloid 2019; 26 (02) 74-84
• 99 Hosoi A, Su Y, Torikai M. et al. Novel antibody for the treatment of transthyretin amyloidosis. J Biol Chem 2016; 291 (48) 25096-25105