Skip to content
How It Works
Explore
Ask a Question Resources Pricing
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 12 peer-reviewed journal articles Updated
Neurology · Hereditary Transthyretin Amyloidosis

Measuring Disease Progress and Staging

At a Glance

Hereditary ATTR amyloidosis staging tracks how disease affects the nerves and heart rather than predicting a fixed timeline. Walking ability, NT-proBNP, eGFR, and sometimes sNfL help clinicians detect changes, compare trends, and guide care.

Staging in hATTR is not a fixed “countdown,” but rather a way for your medical team to measure the current “burden” of the disease on your organs. Because hATTR can affect both your nerves and your heart, doctors use two separate systems to track your progress in each area [1][2]. These stages help them decide when to start or adjust treatments to help slow the disease down [3].

Staging Nerve Damage (Neuropathy)

The most common way doctors describe nerve progression is the Coutinho/FAP Stages. This system focuses primarily on your mobility—your ability to walk and get around [4].

  • Stage I (Mild): You have symptoms like numbness or pain, but you can still walk completely unassisted [4].
  • Stage II (Moderate): You require assistance to walk, such as a cane, crutches, or a walker [4].
  • Stage III (Severe): You are predominantly confined to a wheelchair or bed.

To get a more detailed picture, your doctor may also use the Polyneuropathy Disability (PND) score, which breaks down “walking ability” even further (for example, distinguishing between needing one cane versus two), or the mNIS+7 [5][1]. The mNIS+7 is a composite scorecard that combines physical exams of your strength and reflexes with technical tests of your nerve conduction. Its exact components and maximum score depend on the version used in specific trials, but it is highly sensitive for tracking disease [1][6].

Staging Heart Involvement (Cardiomyopathy)

For the heart, the NAC/Gillmore Staging System is a prognostic standard. It doesn’t rely on how you feel, but on two specific blood markers that show how hard your heart and kidneys are working [2][7].

  1. NT-proBNP: A protein released by the heart when it is under stress or stretched. The threshold for staging is 3,000 ng/L.
  2. eGFR: A measure of how well your kidneys are filtering blood. The threshold is 45 mL/min.
Stage Criteria
Stage I Both markers are “good”: NT-proBNP ≤ 3,000 AND eGFR ≥ 45
Stage II One marker is “abnormal”: Either NT-proBNP > 3,000 OR eGFR < 45
Stage III Both markers are “abnormal”: NT-proBNP > 3,000 AND eGFR < 45

These staging thresholds can be affected by comorbidities. NT-proBNP and eGFR are influenced by atrial fibrillation, kidney disease unrelated to amyloid, age, and body size. They are interpreted as trends in context rather than as a strict rule [2][8].

The Role of sNfL: An Emerging Biomarker

An emerging adjunctive tool in hATTR care is the serum neurofilament light chain (sNfL) test [9]. Neurofilaments are proteins found inside your nerve cells. When a nerve cell is damaged or dies, these proteins “leak” into your bloodstream [9].

Measuring sNfL levels can be incredibly helpful because the levels often start to rise before you notice new symptoms or before standard nerve tests show a change [9][10]. However, there is no universally validated cutoff that automatically proves it is time to start therapy. sNfL is affected by age and kidney function; therefore, a rising result should prompt clinical assessment rather than automatic treatment [11][9].

Why Staging Matters

It is important to remember that these stages describe your organs, not your potential. hATTR is a multisystem disease, and while one system might be in an early stage, another might need more attention [12]. Regular monitoring—which may occur every 6 to 12 months or more frequently—allows your team to catch small changes in these scores and biomarkers early, giving you the best chance to maintain your function and quality of life [3][12].

Common questions in this guide

What do the FAP stages mean for hATTR nerve damage?
The Coutinho/FAP system describes nerve-related disability by walking ability. Stage I means you can walk without help, Stage II means you need a cane, crutches, or walker, and Stage III means you are mostly using a wheelchair or staying in bed. It describes mobility, not every aspect of hATTR.
How is heart involvement staged in hereditary ATTR amyloidosis?
The NAC/Gillmore system uses NT-proBNP, a blood marker of heart strain, and eGFR, a measure of kidney filtering. Stage I means NT-proBNP is 3,000 ng/L or lower and eGFR is 45 mL/min or higher; Stage II means one is outside those ranges, and Stage III means both are outside them. A clinician interprets the results alongside conditions such as atrial fibrillation, kidney disease, age, and body size.
What are PND and mNIS+7 scores used for in hATTR?
PND gives a more detailed description of walking disability, such as whether you need one cane or two. The mNIS+7 combines examinations of strength and reflexes with nerve-conduction testing to track nerve changes over time. The exact mNIS+7 scoring system can vary by version and clinical study.
Can an sNfL blood test detect hATTR nerve damage early?
Serum neurofilament light chain, or sNfL, measures proteins released into the blood when nerve cells are damaged. Levels may rise before new symptoms or changes on standard nerve tests, but there is no universally validated cutoff that automatically means treatment should start. Age and kidney function can affect the result, so a rising level calls for clinical assessment.
Can my nerve stage and heart stage be different?
Yes. hATTR affects multiple body systems, so nerve damage may be at an early stage while heart involvement needs more attention, or the reverse. Your care team tracks both areas separately to understand your overall disease burden and adjust care when needed.
How often should hATTR disease progression be monitored?
Monitoring may occur every 6 to 12 months or more often, depending on your symptoms, test results, and treatment plan. Follow-up can include walking and nerve assessments, heart and kidney blood tests, and sometimes sNfL. Your care team will set the schedule that fits your situation.
How does staging affect hATTR treatment?
Staging helps clinicians decide when to start or adjust treatment intended to slow disease progression, but a stage alone does not determine your care. They also consider symptoms, changes in test results, organ function, and other health conditions when discussing treatment timing.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is my current FAP stage and PND score, and how have these changed since my last visit?
  2. 2.Based on my NT-proBNP and eGFR levels, what is my NAC/Gillmore cardiac stage?
  3. 3.Are we tracking my mNIS+7 score? If so, what does the latest number tell us about my nerve health?
  4. 4.Is serum neurofilament light chain (sNfL) testing available for me to help monitor for early nerve damage?
  5. 5.How do my current staging results influence the choice or timing of my treatment?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (12)
  1. 1

    Development of measures of polyneuropathy impairment in hATTR amyloidosis: From NIS to mNIS + 7.

    Dyck PJB, González-Duarte A, Obici L, et al.

    Journal of the neurological sciences 2019; (405()):116424 doi:10.1016/j.jns.2019.116424.

    PMID: 31445300
  2. 2

    A new staging system for cardiac transthyretin amyloidosis.

    Gillmore JD, Damy T, Fontana M, et al.

    European heart journal 2018; (39(30)):2799-2806 doi:10.1093/eurheartj/ehx589.

    PMID: 29048471
  3. 3

    Early diagnosis of ATTR amyloidosis through targeted follow-up of identified carriers of TTR gene mutations.

    Conceição I, Damy T, Romero M, et al.

    Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 2019; (26(1)):3-9 doi:10.1080/13506129.2018.1556156.

    PMID: 30793974
  4. 4

    A Quantitative Assessment of Upper Limb Motor Function Across Disease Stages in Hereditary Transthyretin Amyloidosis.

    Hamedani M, Prada V, Massucco S, et al.

    Journal of the peripheral nervous system : JPNS 2026; (31(2)):e70127 doi:10.1111/jns.70127.

    PMID: 42246655
  5. 5

    Long-term treatment of hereditary transthyretin amyloidosis with patisiran: multicentre, real-world experience in Italy.

    Gentile L, Mazzeo A, Briani C, et al.

    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2024; (45(9)):4563-4571 doi:10.1007/s10072-024-07494-9.

    PMID: 38622453
  6. 6

    Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis.

    Benson MD, Waddington-Cruz M, Berk JL, et al.

    The New England journal of medicine 2018; (379(1)):22-31 doi:10.1056/NEJMoa1716793.

    PMID: 29972757
  7. 7

    New Advanced Imaging Parameters and Biomarkers-A Step Forward in the Diagnosis and Prognosis of TTR Cardiomyopathy.

    Rimbas RC, Balinisteanu A, Magda SL, et al.

    Journal of clinical medicine 2022; (11(9)) doi:10.3390/jcm11092360.

    PMID: 35566485
  8. 8

    Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy: A Randomized Clinical Trial With Open-Label Extension.

    Adams D, Wixner J, Polydefkis M, et al.

    JAMA neurology 2025; (82(3)):228-236 doi:10.1001/jamaneurol.2024.4631.

    PMID: 39804640
  9. 9

    Longitudinal analysis of serum neurofilament light chain levels as marker for neuronal damage in hereditary transthyretin amyloidosis.

    Berends M, Brunger AF, Bijzet J, et al.

    Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 2024; (31(2)):132-141 doi:10.1080/13506129.2024.2327342.

    PMID: 38477065
  10. 10

    Detailed clinical, physiological and pathological phenotyping can impact access to disease-modifying treatments in ATTR carriers.

    Beauvais D, Labeyrie C, Cauquil C, et al.

    Journal of neurology, neurosurgery, and psychiatry 2024; (95(6)):489-499 doi:10.1136/jnnp-2023-332180.

    PMID: 37875336
  11. 11

    Intracutaneous Amyloid Deposition is Associated With Nerve Conduction Studies Deterioration in Presumed Asymptomatic Pathogenic Variant TTR Carriers.

    Schulz N, Beauvais D, Cauquil C, et al.

    European journal of neurology 2025; (32(7)):e70277 doi:10.1111/ene.70277.

    PMID: 40653952
  12. 12

    Optimal practices for the management of hereditary transthyretin amyloidosis: real-world experience from Japan, Brazil, and Portugal.

    Ando Y, Waddington-Cruz M, Sekijima Y, et al.

    Orphanet journal of rare diseases 2023; (18(1)):323 doi:10.1186/s13023-023-02910-3.

    PMID: 37828588

This page explains how hATTR staging tests track nerve and heart involvement for informational purposes only and does not constitute medical advice. Your care team should interpret your results in context.

Get notified when new evidence is published on Hereditary ATTR amyloidosis.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.