hATTR Pathology: Nerve Biopsy Results from Italian Referral Centers

• Main Authors: Marco Luigetti, Marina Romozzi, Giulia Bisogni, Davide Cardellini, Tiziana Cavallaro, Andrea Di Paolantonio, Gian Maria Fabrizi, Silvia Fenu, Luca Gentile, Marina Grandis, Gianluca Marucci, Sara Massucco, Anna Mazzeo, Davide Pareyson, Angela Romano, Massimo Russo, Angelo Schenone, Matteo Tagliapietra, Stefano Tozza, Giuseppe Vita, Mario Sabatelli
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Brain Sciences
• Subjects: hATTR; nerve biopsy; amyloid; Congo red; axonal loss; polyneuropathy
• Online Access: https://www.mdpi.com/2076-3425/10/11/780

Pathological evidence of amyloid on nerve biopsy has been the gold standard for diagnosis in hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN) for a long time. In this article, we reviewed the pathological findings of a large series of sural nerve biopsies from a cohort of hATTR-PN patients, collected by different Italian referral centers. <b>Patients and Methods:</b> We reviewed clinical and pathological data from hATTR-PN patients, diagnosed and followed in five Italian referral centers for peripheral neuropathies. Diagnosis was formulated after a positive genetic test for transthyretin (<i>TTR</i>) mutations. Sural nerve biopsy was performed according to standard protocols. <b>Results:</b> Sixty-nine sural nerve biopsies from hATTR-PN patients were examined. Congo red positive deposits were found in 73% of cases. Only the Phe64Leu mutation failed to show amyloid deposits in a high percentage of biopsies (54%), as already described. Unusual pathological findings, such as myelin abnormalities or inflammatory infiltrates, were detected in occasional cases. <b>Conclusions:</b> Even if no longer indicated to confirm hATTR-PN clinical suspicion, nerve biopsy remains, in expert hands, a rapid and inexpensive tool to detect amyloid deposition. In Italy, clinicians should be aware that a negative biopsy does not exclude hATTR-PN, particularly for Phe64Leu, one of the most frequent mutations in this country.