Table 3.

Diagnostic tools for ATTR-PN

	TTR gene analysis	Amyloid detection
		Biopsya	DPD, PYP, HMDP scintigraphy
Advantages	Looking for 1 of the 130 amyloidogenic variants [10] Possible to rule out ATTRv if gene analysis is negative for a variant Fastest method to confirm ATTRv in case of neuropathy	Formal proof of amyloidosis in carriers of TTR variants and sporadic amyloid neuropathy	Noninvasive demonstration of cardiac amyloid with bone scintigraphy [43, 44]
Rules	TTR gene sequencing of the 4 exons	Congo red staining Examination under polarized microscopy Many sections often needed to detect a single deposit
Limits	13 nonamyloidogenic variants, including Gly6Ser and Thr119Met [10] Possible delay of genetic results	Sensitivity for amyloid detection 60–80% [25] Dependent on experience and expertise of pathologist May be invasive and risky (cardiac) Time-consuming Several biopsy sites sometimes needed to find a deposita	Radiolabeling if no light chain Sensitivity < 100% LV wall thickness > 12 mm in combination with abnormal heart/whole-body retention Heart/whole-body > 7.5 associated with the highest event rate [45]
Remarks	Some correlation between mutation and predominant organ involvement (e.g., heart, brain, eye)	False negative Amyloid light chain must be excluded	Complementarity of TTR gene analysis May avoid cardiac biopsy

ATTR-PN amyloid transthyretin polyneuropathy, DPD diphosphono-1,2-propanodicarboxylic acid, HMDP hydroxymethylene diphosphonate, LV left ventricular, PYP pyrophosphate

^aAt least one tissue biopsy should be performed to identify amyloid deposits and, if negative, another biopsy, preferentially mini-invasive (skin, labial salivary gland, abdominal fat), should be performed