hATTR amyloidosis: a life-threatening, multisystem disease that causes significant burden1,2

The disease affects multiple organs, resulting in varying symptoms3

Because amyloids are deposited at multiple sites in the body, including the nerves, heart, and gastrointestinal tract, patients with hereditary transthyretin-mediated (hATTR) amyloidosis can present with a range of sensory and motor, autonomic, and cardiac symptoms.3-5

Most common clinical manifestations

Sensory-motor neuropathy3,4

  • Pain, tingling
  • Altered sensation
  • Bilateral carpal tunnel syndrome
  • Weakness
  • Difficulty walking

Autonomic neuropathy3,4

  • Orthostatic hypotension
  • Diarrhea, constipation, nausea and vomiting
  • Unintentional weight loss

Cardiac manifestations5

  • Conduction abnormalities
  • Arrhythmias
  • Heart failure

Additional signs4

  • Rapid symptom progression
  • Family history of the disease or hATTR amyloidosis symptoms
  • Failure to respond to immunomodulatory treatment
  • Intolerance of commonly used cardiovascular medications
Other symptoms of the disease

Ocular manifestations4

  • Vitreous opacification
  • Glaucoma
  • Abnormal conjunctival vessels
  • Papillary abnormalities


  • Proteinuria
  • Renal failure

CNS manifestations4

  • Progressive dementia
  • Headache
  • Ataxia
  • Seizures
  • Spastic paresis
  • Stroke-like episodes

Many patients present with multisystem dysfunction3

Symptom presentation varies by mutation, and patients can present with a range of sensory, motor, autonomic, and cardiac symptoms3

Phenotype varies by mutation6,a,b

Percentage of patients with hATTR amyloidosis who have sensory neuropathy, motor neuropathy, GI symptoms, or cardiac complications
THAOS=Transthyretin Amyloidosis Outcomes Survey.
  1. Not representative of all possible TTR gene mutations.
  2. Data collected by the THAOS registry.

Symptoms of hATTR amyloidosis can progress quickly, leading to significant disability2,3

Although every patient is different, the progression of length-dependent sensory-motor neuropathy may follow the same general course.
FAP stage and PND score can be used to assess polyneuropathy progression in your patients.

Select FAP or PND below to learn more about each scoring system.

Clinical staging system as described by Coutinho et al, according to sensory and motor neuropathy progression.2

Stage Description
Stage 0

No symptoms of sensory or motor neuropathy

Stage 1

Unimpaired ambulation; mostly mild sensory, motor, and autonomic neuropathy in the lower limbs

Stage 2

Assistance with ambulation required; mostly moderate impairment progression to the lower limbs, upper limbs, and trunk

Stage 3

Wheelchair-bound or bedridden; severe sensory, motor, and autonomic involvement of all limbs

Modified PND scoring system first described by Yamamoto et al, to assess the polyneuropathy in patients with hATTR amyloidosis.7

Stage Description
Stage 0

No symptoms of neuropathy

Stage 1

Sensory disturbances but preserved walking capability

Stage 2

Impaired walking capacity but ability to walk without a stick or crutches

Stage 3

A: Walking with the help of one stick or crutch
B: Walking with the help of two sticks or crutches

Stage 2

Confined to a wheelchair or bedridden

Symptoms of hATTR amyloidosis can negatively impact a patient’s quality of life

Decline in function2,5

  • Inability to walk unaided
  • Wheelchair-bound or bedridden
  • Increased risk of hospitalization

Impact on daily life8-11

  • Inability to work
  • Pain/discomfort performing usual activities
  • Increased dependence on caregiver(s)

Social burden12

  • Interference with social activities
  • Anxiety and depression
The considerable burden patients experience makes an early and accurate diagnosis critical.4,13,14

Take the mystery case diagnosis challengeThis useful tool is designed to help you recognize the red-flag symptoms of hATTR amyloidosis. Start the challenge

Are symptoms and family history leading you to suspect hATTR amyloidosis?Your patient may be eligible for Alnylam Act®, a genetic testing and counseling program available at no charge.
Download application now


  1. Swiecicki PL, Zhen DB, Mauermann ML, et al. Amyloid. 2015;22(2):123-131.
  2. Coutinho P, Martins da Silva A, Lopes Lima JL, et al: Excerpta Medica; 1980:88-98.
  3. Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.
  4. Conceição I, González-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21(1):5-9.
  5. Dharmarajan K, Maurer MS. J Am Geriatr Soc. 2012;60(4):765-774.
  6. Wixner J, Mundayat R, Karayal ON, et al. Orphanet J Rare Dis. 2014;9:61.
  7. Yamamoto S, Wilczek HE, Nowak G, et al. Am J Transplant. 2007;7(11):2597-2604.
  8. Vinik EJ, Vinik AI, Paulson JF, et al. J Peripher Nerv Syst. 2014;19:104-119.
  9. Vinik EJ, Hayes RP, Oglesby A, et al. Diabetes Technol Ther. 2005;7(3):497-508.
  10. Pruppers MHJ, Merkies ISJ, Faber CG, et al. J Peripher Nerv Syst. 2015;20(3):319-327.
  11. Berk J, Lin H, Agarwal S, et al. Poster presented at: XVIth International Symposium on Amyloidosis (ISA); March 26-29, 2018; Kumamoto, Japan.
  12. Lopes A, Fonseca I, Sousa A, et al. Amyloid. 2018;25(1):26-36.
  13. Gertz MA. Am J Manag Care. 2017;23(suppl 7):S107-S112.
  14. Obici L, Kuks JB, Buades J, et al. Curr Opin Neurol. 2016;29(suppl 1):S27-S35.
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