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

hATTR amyloidosis is a multisystem disease which primarily causes symptoms of polyneuropathy (sensory-motor neuropathy and autonomic neuropathy) and cardiac manifestations3,4

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 neuropathy3,5

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

Autonomic neuropathy3,5

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

Cardiac manifestations6

  • Conduction abnormalities
  • Arrhythmias
  • Heart failure
Other symptoms of the disease

Ocular manifestations5

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

Nephropathy5

  • Proteinuria
  • Renal failure

CNS manifestations5

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

Additional signs5

  • Rapid symptom progression
  • Family history of the disease or hATTR amyloidosis symptoms
  • Failure to respond to immunomodulatory treatment
  • Intolerance of commonly used cardiovascular medications
Certain factors are associated with rapid disease progression and poor outcomes: advanced age, non-V30M mutation, and multisystem involvement.7-9

Many patients present with multisystem dysfunction3

Patients can present with a range of sensory, motor, autonomic, and cardiac symptoms3

Phenotype by mutation10,a,b

Percentage of patients with hATTR amyloidosis who have sensory neuropathy, motor neuropathy, GI symptoms, or cardiac manifestations
  • aNot representative of all possible TTR gene mutations.
  • bData collected by the THAOS registry.
  • hTHAOS=Transthyretin-Associated Amyloidosis Outcomes Survey.
Despite historical categorizations based on predominant phenotype, hATTR amyloidosis is one disease with multiple manifestations.3,4

Progression of polyneuropathy leads to significant disability2,3

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 progression2

Stage Description
Familial Amyloid Polyneuropathy (FAP) Stage 0

No symptoms of sensory or motor neuropathy

Familial Amyloid Polyneuropathy (FAP) Stage 1

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

Familial Amyloid Polyneuropathy (FAP) Stage 2

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

Familial Amyloid Polyneuropathy (FAP) 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 amyloidosis11

Stage Description
Polyneuropathy Disability (PND) Score 0

No symptoms of neuropathy

Polyneuropathy Disability (PND) Score 1

Sensory disturbances but preserved walking capability

Polyneuropathy Disability (PND) Score 2

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

Polyneuropathy Disability (PND) Score 3

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

Polyneuropathy Disability (PND) Score 4

Confined to a wheelchair or bedridden

Symptoms of hATTR amyloidosis can negatively impact the quality of a patients life

Decline in function2,6

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

Impact on daily life12-15

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

Social burden16

  • Interference with social activities
  • Anxiety and depression
The considerable burden patients experience makes an early and accurate diagnosis critical.4,5,17

Take the mystery case diagnosis challenge This 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.
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References:

  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. Gertz MA. Am J Manag Care. 2017;23(Suppl 7):S107-S112.
  5. Conceição I, González-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21(1):5-9.
  6. Dharmarajan K, Maurer MS. J Am Geriatr Soc. 2012;60(4):765-774.
  7. Planté-Bordeneuve V, Gorram F, Salhi F, et al. J Neurol.2017;264(2):268-276.
  8. Sattianayagam PT, Hahn AF, Whelan CJ, et al. Eur Heart J . 2012;33(9):1120-1127.
  9. Carvalho A, Rocha A, Lobato L. Liver Transpl. 2015;21(3):282-292.
  10. Wixner J, Mundayat R, Karayal ON, et al. Orphanet J Rare Dis. 2014;9:61.
  11. Yamamoto S, Wilczek HE, Nowak G, et al. Am J Transplant. 2007;7(11):2597-2604.
  12. Vinik EJ, Vinik AI, Paulson JF, et al. J Peripher Nerv Syst. 2014;19:104-119.
  13. Vinik EJ, Hayes RP, Oglesby A, et al. Diabetes Technol Ther. 2005;7(3):497-508.
  14. Pruppers MHJ, Merkies ISJ, Faber CG, et al. J Peripher Nerv Syst. 2015;20(3):319-327.
  15. Berk J, Lin H, Agarwal S, et al. Poster presented at: XVIth International Symposium on Amyloidosis (ISA); March 26-29, 2018; Kumamoto, Japan.
  16. Lopes A, Fonseca I, Sousa A, et al. Amyloid. 2018;25(1):26-36.
  17. Obici L, Kuks JB, Buades J, et al. Curr Opin Neurol. 2016;29(suppl 1):S27-S35.
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