Hereditary ATTR amyloidosis: a progressive and life-threatening familial disease1-3

What is hATTR amyloidosis?

hATTR amyloidosis is an autosomal dominant disease caused by a mutation in the transthyretin (TTR) gene that results in misfolded TTR proteins accumulating as amyloid fibrils in multiple sites including the nerves, heart, and GI tract.2,4,5

Formation of amyloid fibrils2,4-6
TTR mutation leads to protein misfolding and formation of amyloid fibrils that are deposited at multiple sites in the body

hATTR amyloidosis affects an estimated 50,000 patients worldwide5

In the disease continuum of hATTR amyloidosis, some patients present primarily with polyneuropathy symptoms, historically known as familial amyloidotic polyneuropathy (FAP), and other patients present primarily with cardiomyopathy symptoms, historically known as familial amyloidotic cardiomyopathy (FAC). A substantial proportion of patients present with a mixed phenotype that includes sensory and motor, autonomic, and cardiac symptoms.5,7-9

The symptom presentation of hATTR amyloidosis is highly varied among patients, even within the same mutation or the same family. In addition to the varied symptom presentation, age of onset varies among patients—with a median age of 39 years, with some presenting as early as their 20s.7,10

As the disease progresses, symptoms of hATTR amyloidosis increase in severity and may eventually rob patients of function—and even their lives.1-3

hATTR amyloidosis can lead to significant morbidity, disability, and mortality.1-3,11

References:

  1. 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.
  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. Damy T, Judge DP, Kristen AV, et al. Cardiac findings and events observed in an open-label clinical trial of tafamidis in patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis. J Cardiovasc Transl Res. 2015;8(2):117-127.
  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. Sekijima Y. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J Neurol Neurosurg Psychiatry. 2015;86(9):1036-1043.
  7. Ando Y, Coelho T, Berk JL, et al. Guidelines of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013;8:31.
  8. 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.
  9. 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.
  10. Coelho T, Maurer MS, Suhr OB. THAOS—The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013;29(1):63-76.
  11. Castaño 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.