Help accelerate the diagnosis of hATTR amyloidosis

Process for ensuring a timely diagnosis

Due to the rapid natural progression of the disease, patients with hATTR amyloidosis require an early and accurate diagnosis.^1-3

Raise clinical suspicion

Recognize red-flag symptoms of sensory-motor neuropathy, autonomic neuropathy, and cardiac manifestations
Identify a family history of hATTR amyloidosis symptoms

View the red-flag symptoms

Identify the signs through diagnostic tools^a

Several types of tests can help identify the signs of hATTR amyloidosis

Select an assessment below to learn more about the diagnostic tools and results

Electromyography (EMG)Electro- myography (EMG)	Fibrillation potentials and positive sharp waves signifying axonal injury and active denervation Volitional motor unit recruitment consistent with chronic denervation and reinnervation
Nerve conduction study (NCS)	Axonal large-fiber polyneuropathy with greater sensory involvement than motor Absent or reduced sensory nerve conduction amplitudes Reduced or absent motor nerve conduction amplitudes with normal to mildly slowed conduction velocities
Quantitative sudomotor axon reflex test (QSART)	Diminished sweat volume
Sympathetic skin response (SSR)	Reduced amplitude in response to electrical stimuli

Heart rate deep breathing	Limited heart rate variability in response to deep breathing
Tilt table	Orthostatic hypotension in response to upright tilt
Valsalva maneuver	Rapid blood pressure decline in response to exhalation against a closed airway
Quantitative sudomotor axon reflex test (QSART)	Diminished sweat volume
Sympathetic skin response (SSR)	Reduced amplitude in response to electrical stimuli

Echocardiography	Left ventricular wall thickening Refractile myocardium (granular sparkling) Low tissue Doppler velocities, reduced longitudinal strain that may be more pronounced at the base than the apex
Electrocardiography (ECG)	Low voltage Pseudo-infarction pattern Progressive reduction in QRS voltage over time Atrioventricular (AV) block
Cardiac magnetic resonance imaging (CMRI)	Left ventricular wall thickening Subendocardial late gadolinium enhancement

It is also important to remember that the symptoms of hATTR amyloidosis may overlap with those of other diseases. A detailed diagnostic history may help to identify patients with hATTR amyloidosis.

Common misdiagnoses in patients with hATTR amyloidosis^2,5,6,9-20

Clinical manifestations and/or diagnostic findings	Potential diagnoses
Ataxia and foot numbness	CIDP
Motor involvement	ALS Motor polyradiculoneuropathyMotor polyradiculoneuro- pathy
Pain and tingling with alcohol abuse	Alcoholic neuropathy
Upper limb neuropathy	Carpal tunnel syndrome Idiopathic polyneuropathy Paraneoplastic neuropathy CIDP Motor neuron diseases
Weakness in feet, ankles, legs	Charcot-Marie-Tooth disease (CMT)
Polyneuropathy with diabetes	Diabetic polyneuropathy
Polyneuropathy with evidence of amyloid deposition	AL amyloidosis AA amyloidosis
Left ventricular hypertrophy	Hypertensive heart disease Hypertrophic cardiomyopathy Fabry disease AL amyloidosis wtATTR amyloidosis
Diastolic dysfunction
Heart failure with preserved ejection fraction

AA=amyloid A; AL=amyloid light chain; ALS=amyotrophic lateral sclerosis; CIDP=chronic inflammatory demyelinating polyneuropathy; wtATTR=wild-type ATTR.

See 2 examples of patients with hATTR amyloidosis you might encounter in your practice. Download now

Options to help confirm a diagnosis^5,7,9,a

Genetic testing

Detection of a mutation in the TTR gene

Scintigraphy

Cardiac uptake of ^99mTc-PYP or ^99mTc-DPD

Tissue biopsy

Green birefringence under polarized light when stained with Congo red

^99mTc-DPD=technetium-^99m-3,3-diphosphono-1,2-propanodicarboxylic acid;^99mTc-PYP=technetium-^99mpyrophosphate.

^aNot a comprehensive list of diagnostic tools.

Genetic testing through Alnylam Act^®

Third-party genetic testing and counseling programs offered at no charge^a

Genetic testing and counseling may help to:

Identify risk of disease for patients and their family members
Shorten the time to diagnosis and prevent misdiagnoses
Determine if patients are eligible to participate in clinical trials
Provide information about support resources such as patient advocacy organizations

Find out more about Alnylam Act^® or order a test

^aThe Alnylam Act^® program was developed to reduce barriers to genetic testing and counseling to help people make more informed decisions about their health. While Alnylam provides financial support for this program, tests and services are performed by independent third parties. Healthcare professionals must confirm that patients meet certain criteria to use the program. Alnylam receives de-identified patient data from this program, but at no time does Alnylam receive patient identifiable information. Alnylam receives contact information for healthcare professionals who use this program. Genetic testing is available in the U.S. and Canada. Genetic counseling is only available in the U.S. Healthcare professionals who use this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use or support any Alnylam product.

References:

Gertz MA. Am J Manag Care. 2017;23(suppl 7):S107-S112.
Conceição I, González-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21(1):5-9.
Obici L, Kuks JB, Buades J, et al. Curr Opin Neurol. 2016;29(suppl 1):S27-S35.
Shin SC, Robinson-Papp J. Mt Sinai J Med. 2012;79(6):733-748.
Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.
Castro J, Miranda B, Castro I, et al. Clin Neurophysiol. 2016;127(5):2222-2227.
Dharmarajan K, Maurer MS. J Am Geriatr Soc. 2012;60(4):765-774.
Falk RH, Quarta CC. Heart Fail Rev. 2015;20(2):125-131.
Adams D, Suhr OB, Hund E, et al. Curr Opin Neurol. 2016;29(suppl 1):S14-S26.
Goyal NA, Mozaffar T. Neurol Genet. 2015;1:e18.
Zeng L, Alongkronrusmee D, van Rijn RM. J Pain Res. 2017;10:219-228.
Cortese A, Vegezzi E, Lozza A, et al. J Neurol Neurosurg Psychiatry. 2017;88(5):457-458.
Adams D, Lozeron P, Lacroix C. Curr Opin Neurol. 2012;25(5):564-572.
Szigeti K, Lupski JR. Eur J Hum Genet. 2009;17(6):703-710.
Hovaguimian A, Gibbons CH. Curr Pain Headache Rep. 2011;15(3):193-200.
Rapezzi C, Longhi S, Milandri A, et al. Amyloid. 2012;19(suppl 1):16-21.
Linhart A. In: Mehta A, Beck M, Sunder-Plassmann G (eds). Oxford: Oxford PharmaGenesis; 2006. Chapter 20.
Lalande S, Johnson BD. Drugs Today (Barc). 2008;44(7):503-513.
Ruberg FL, Berk JL. Circulation. 2012;126(10):1286-1300.
Kapoor M, Rossor AM, Jaunmuktane Z, et al. Pract Neurol. 2018. 0:1-9. doi:10.1136/practneurol-2018-002098.

Help accelerate the diagnosis of hATTR amyloidosis

Process for ensuring a timely diagnosis

Raise clinical suspicion

View the red-flag symptoms

Identify the signs through diagnostic toolsa

Select an assessment below to learn more about the diagnostic tools and results

Common misdiagnoses in patients with hATTR amyloidosis2,5,6,9-20

See 2 examples of patients with hATTR amyloidosis you might encounter in your practice. Download now

Options to help confirm a diagnosis5,7,9,a

Genetic testing

Scintigraphy

Tissue biopsy

Genetic testing through Alnylam Act®

Third-party genetic testing and counseling programs offered at no chargea

Find out more about Alnylam Act® or order a test

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Third Party Sites

Identify the signs through diagnostic tools^a

Common misdiagnoses in patients with hATTR amyloidosis^2,5,6,9-20

Options to help confirm a diagnosis^5,7,9,a

Genetic testing through Alnylam Act^®

Third-party genetic testing and counseling programs offered at no charge^a

Find out more about Alnylam Act^® or order a test