Hereditary ATTR amyloidosis with polyneuropathy is under-recognized, debilitating, and progressive, and early diagnosis is critical1-4
POLYNEUROPATHY MANIFESTATIONS
The polyneuropathy of hereditary ATTR amyloidosis can manifest in a variety of ways
Peripheral sensorimotor neuropathy3
- Numbness, tingling, swelling, burning, and other abnormal feelings in hands and feet
- Neuropathic pain
- Walking disability
- Loss of balance
Autonomic neuropathy2
- Orthostatic hypotension
- Diarrhea and constipation that may alternate
- Early satiety
- Sweating abnormalities
- Urinary retention associated with incontinence
- Erectile dysfunction
Patients may present with a range of signs and symptoms including polyneuropathy, cardiomyopathy, bilateral carpal tunnel syndrome, lumbar spinal stenosis, nephropathy, gastrointestinal disturbances, and ocular manifestations, among others. Patients with hereditary ATTR amyloidosis may present with a mixed phenotype, including both polyneuropathy and cardiomyopathy.2,3,5*
*TEGSEDI is not approved for and has not been shown to be safe and effective for the treatment of cardiomyopathy in patients with hereditary ATTR amyloidosis. The NEURO-TTR study was not designed to assess the impact of TEGSEDI on cardiomyopathy symptoms.
Abbreviations: ATTR, transthyretin-mediated amyloidosis; hATTR-PN, hereditary transthyretin-mediated amyloidosis with polyneuropathy.
Due to the systemic nature of hereditary ATTR amyloidosis, it is imperative to perform a complete workup of diagnosed patients for all potential manifestations2

Disease progression
The polyneuropathy of hereditary ATTR amyloidosis can progress rapidly if left undiagnosed or untreated1,4
Progression of FAP6
Abbreviations: FAP, familial amyloid polyneuropathy; PND, polyneuropathy disability.
- The hereditary nature of the disease is particularly challenging for families who have observed the progressive decline of family members3
- Without treatment, patients will experience greater difficulty with daily tasks (eg, turning a key in a lock or fastening buttons on clothing) and walking will become more difficult3

Before I became symptomatic, I was very active. I used to love riding my bicycle, dancing, racing motorcycles, so it was devastating when I couldn’t do these things anymore due to my condition.
Chuck | Patient living with the polyneuropathy of hereditary ATTR amyloidosis and taking TEGSEDI

I have come to believe that perhaps my cardiac issues may have sort of masked other issues that were probably brewing behind the scenes… I began to develop symptoms of polyneuropathy including GI issues.
Lane | Patient living with the polyneuropathy of hereditary ATTR amyloidosis and taking TEGSEDI
Mechanism of disease
Hereditary ATTR amyloidosis with polyneuropathy is characterized by the deposition of amyloid fibrils throughout the body, including the nerves2
-
Liver
The TTR protein is primarily synthesized by the liver.1,7
-
TTR tetramer
TTR proteins are excreted from the liver as tetramers.1,7
-
TTR monomer
Tetramers dissociate into monomers due to TTR gene mutations.1,7
-
Misfolded TTR proteins
Monomers can misfold and aggregate into fibrils.1,7
-
Amyloid fibrils
Amyloid fibrils can deposit in various organs and cause systemic dysfunction.1,7
- The aggregation of amyloid in organs and tissues, including nerves, causes the symptoms of hereditary ATTR amyloidosis1,7
Abbreviation: TTR, transthyretin.
Hereditary ATTR amyloidosis with polyneuropathy has significant morbidity and can have debilitating physical symptoms that significantly impact patients’ QoL2,3

Suspect and diagnose
Look for red-flag symptoms in patients with peripheral sensorimotor neuropathy
Suspect and diagnose hereditary ATTR amyloidosis with polyneuropathy early by looking for clusters of the following findings2,8:
Family history of hereditary ATTR amyloidosis
Bilateral carpal tunnel syndrome
Vitreous opacities
Renal abnormalities
Cardiovascular manifestations
- Chronic heart failure
- Ventricular wall thickening with preserved ejection fraction
- Conduction disturbances/syncope
GI symptoms that may be uncontrollablea
- Diarrhea
- Constipation
- Alternating diarrhea and constipation
- Unexplained weight loss
Autonomic conditions
- Orthostatic hypotension
- Urinary retention leading to recurrent urinary tract infections
- Sexual dysfunction
- Sweating abnormality
Additional alert signs and symptoms
- Rapid disease progression
- Failure to respond to prior therapies for another diagnosis
Abbreviation: GI, gastrointestinal.
aGI symptoms may result from autonomic neuropathy and/or amyloid deposition within the gastrointestinal tract.2,4
Look for clusters of symptoms in your patients with sensorimotor neuropathy to identify hereditary ATTR amyloidosis with polyneuropathy as early as possible2,9
Identify patients who may be appropriate for treatment with TEGSEDI
Manifestations of polyneuropathy
- Signs and symptoms can include sensory, motor, and autonomic neuropathy2
- FAP staging and PND scoring can assess patients’ neuropathic impairment at time of treatment initiation6
Genetic confirmation of hereditary ATTR amyloidosis
- Diagnosis can include assessment of clinical symptoms and evidence of amyloid deposition, and ultimately requires a genetic test3,10
- ICD-10-CM code for hereditary ATTR amyloidosis is E85.1
TEGSEDI is indicated for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.11
TEGSEDI is contraindicated in patients with11
- Platelet count below 100 × 109/L
- History of acute glomerulonephritis caused by TEGSEDI
- History of a hypersensitivity reaction to TEGSEDI
Genetic testing with hATTR Compass can confirm a diagnosis of hereditary ATTR amyloidosis with polyneuropathy early to optimize management1,3,10
