Table 4.

TTR-FAP stages of disease according to symptom severity

Stage of disease	Symptoms	PND	Treatment suggestions	Comments
Stage 0	Asymptomatic		Follow-up according to patient's age and mutation type
Stage I	Mild, ambulatory, symptoms at lower limbs limited	I. Sensory disturbances in extremities but preserved walking capacity	Confirm diagnosis	Best candidates for liver transplant are early onset Met30 (young with mild symptoms)
		II. Difficulties in walking but without the need for a walking stick	First-line pharmacotherapy: tafamidis (EU approved) or diflunisal if not available
			Liver transplant
			Follow up every 6 months for disease progression, especially cardiac
Stage II	Moderate, further neuropathic deterioration, ambulatory but requires assistance	IIIa. One stick or one crutch required for walking	Diflunisal may slow progression of the disease
		IIIb. Two sticks or two crutches required for walking
Stage III	Severe, bedridden/wheelchair-bound with generalized weakness	IV. Patient confined to a wheelchair or bed	No evidence for pharmacotherapy
			Treatment through clinical trial
Recommended assessments
Neuropathic: Modified Norris score, modified polyneuropathy disability (PND) score, neuropathy impairment score-weakness score (onset of orthostatic hypotension ++), scintigraphy with metaiodobenzylguanidine (mIBG)
Electrophysiological: Quantitative sensation tests, quantitative autonomic tests, electromyographic test, sympathetic skin response
Cardiac: ECG, Holter ECG, BNP/NT-proBNP, troponin, and echocardiography. When necessary: MRI, ‘bone’ DPD scintigraphy, intracardiac electrophysiological study
Renal: Urinalysis
General: Physical and clinical examination include weight (body mass index), blood test including s-albumin, quality of life

BNP, brain natriuretic peptide; DPD, 3,3-diphosphono-1,2-propanodicarboxylic acid; ECG, electrocardiography; NT-proBNP, N-terminal of the prohormone BNP; TTR-FAP, transthyretin familial amyloid polyneuropathy. Adapted from [3,30,31].