The disease affects multiple organs, resulting in varying symptoms^1,3,4

Because amyloid fibrils are deposited in tissues throughout the body, including the nerves, heart, and GI tract, patients with hATTR amyloidosis can present across a spectrum that includes sensory and motor, autonomic, and cardiac symptoms.^1-5

In fact, more than half of patients with hATTR amyloidosis present with a mixed phenotype.^6,7

Symptom presentation is highly varied among patients, even within the same mutation. Symptoms can also vary among patients in the same family⁸

Symptoms of hATTR amyloidosis can progress quickly, leading to life-threatening dysfunction^2,3,9

As the disease progresses, symptoms increase in severity, leading to significant disability, decreased quality of life, and premature death.^9,10  hATTR amyloidosis can lead to mortality within 2 to 15 years.^2,3,9,11

Due to the variability of the disease, progression of symptoms can also be considerably different from patient to patient.⁸

References:

1. Conceição I, González-Duarte A, Obici L, et al. “Red-flag” symptom clusters in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2016;21(1):5-9.
2. Hanna M. Novel drugs targeting transthyretin amyloidosis. Curr Heart Fail Rep. 2014;11(1):50-57.
3. Mohty D, Damy T, Cosnay P, et al. Cardiac amyloidosis: updates in diagnosis and management. Arch Cardiovasc Dis. 2013;106(10):528-540.
4. Shin SC, Robinson-Papp J. Amyloid neuropathies. Mt Sinai J Med. 2012;79(6):733-748.
5. Hawkins PN, Ando Y, Dispenzeri A, et al. Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015;47(8):625-638.
6. Rapezzi C, Quarta CC, Obici L, et al. Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective. Eur Heart J. 2013;34(7):520-528.
7. Adams D, Gonzalez-Duarte A, O’Riordan W, et al., An investigational RNAi therapeutic for the treatment of hereditary ATTR amyloidosis with polyneuropathy: baseline demographics from the phase 3 APOLLO study. In: The XVth International Symposium on Amyloidosis. Uppsala, Sweden: ISA International Society of Amyloidosis; July 3-7, 2016. PA 82.
8. Ando Y, Coelho T, Berk JL, et al. Guidelines of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013;8:31.
9. Adams D, Coelho T, Obici L, et al., Rapid progression of familial amyloidotic polyneuropathy: a multinational natural history study. Neurology. 2015;85(8):675-682.
10. Adams D, Suhr OB, Hund E, et al. First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy. Curr Opin Neurol. 2016;29(suppl 1):S14-S26.
11. Castano A, Drachman BM, Judge D, et al. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015;20(2):163-178.