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Table 2 Follow-up methods for TTR gene mutation carriers in Japan, Brazil, and Portugal

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

 

Japan

Brazil and Portugal

Timing to initiate follow-up before the disease onset

Early-onset: when the genetic test reveals a positive result

Late-onset: 10 years prior to the predicted age of onset (predicted based on the family history)a, annually after a positive genetic test

Methods to follow-up before the disease onset

Early-onset: annual noninvasive tests, annual biopsy

Late-onset: annual noninvasive tests (frequency can be increased at the physician’s discretion). Biopsy can be scheduled at the physician’s discretion

Annual noninvasive tests (frequency can be increased at the physician’s discretion)

Position of noninvasive tests and biopsies in diagnosis

Auxiliary diagnosis by noninvasive tests such as scintigraphy is useful, but the final definitive diagnosis is made by biopsy

Bone scintigraphy grade 2 or 3 sometimes replaces biopsy in late-onset cases with myocardiopathy

Main biopsy sites

Early-onset: abdominal fat (if not available, other less invasive sites can be selected)

Late-onset: abdominal skin

Salivary glands, skin

Purpose of biopsy

To detect amyloid deposits before the symptom onset

To establish a definitive diagnosis

To establish a definitive diagnosis (if the result is negative and the suspected diagnosis remains, another biopsy is scheduled after 3–6 months)

Types of noninvasive tests

Medical interview (sensation, movement, autonomic nerve function [orthostatic hypotension, gastrointestinal symptoms, and dysuria], weight loss, heart failure, arrhythmia, and ocular symptoms), physical examination (neurological, autonomic, cardiac, gastrointestinal, and ocular symptoms), blood tests (BNP or NT-proBNP, troponin T, transthyretin, albumin, creatinine, TSH, free T3, and free T4), renal function (eGFR and urinary microalbumin), blood pressure, cardiac evaluation (ECG [R-R interval]), Holter ECG, echocardiography, and 99mTc-PYP myocardial scintigraphy), and ophthalmologic examination

Clinical evaluation (NIS, spine vs orthostatic blood pressure, and BMI), neurophysiology tests (nerve conduction study, sudomotor test [Sudoscan™], HRDB or heart rate variability, and QST), blood/urine biomarker tests (NT-proBNP, troponin, and others), and cardiac evaluation (99mTc-DPD myocardial scintigraphy, MRI, echocardiography, and ECG)

References

[7]

[11]

  1. The data were based on the collation of discussions from a medical advisory board meeting attended by amyloidosis specialists in Japan, Brazil, and Portugal. “Early-onset” represents individuals originating from kindred with early-onset disease, and “late-onset” represents those originating from kindred with late-onset disease
  2. aThe age at onset may differ between the affected parent and child, especially in mother-son pairs [42]
  3. 99mTc-DPD 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-PYP 99mtechnetium-pyrophosphate, BMI body mass index, BNP brain natriuretic peptide, ECG electrocardiography, eGFR estimated glomerular filtration rate, HRDB heart rate response to deep breathing, MRI magnetic resonance imaging, NIS Neuropathy Impairment Score, NT-proBNP N-terminal pro-brain natriuretic peptide, QST quantitative sensory testing, T3 triiodothyronine, T4 thyroxine, TSH thyroid-stimulating hormone, TTR transthyretin
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Orphanet Journal of Rare Diseases

ISSN: 1750-1172