To compare the sensitivity of nerve biopsy, fat aspirate and skin biopsy in detecting amyloid deposits in symptomatic hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN).

Previous studies have analyzed the diagnostic sensitivity of abdominal fat aspiration in cardiac ATTRv and skin biopsy for ATTRv-PN. None have analyzed and compared the sensitivity of fat aspirate, skin biopsy and nerve biopsy for ATTRv-PN.

We performed an electronic chart review to identify patients with ATTRv-PN (2012-2023) seen at our institution. Patients with neuropathic symptoms and PN confirmed by a neurologist or EMG that underwent a fat aspirate, skin biopsy (two sites) or nerve biopsy were included. All patients had a pathogenic variant in the TTR gene and either a tissue biopsy positive for amyloidosis or a positive pyrophosphate cardiac scintigraphy scan. Demographics, clinical, laboratory and pathologic data were reviewed.

Of 198 patients with symptomatic ATTRv-PN seen at one of the Mayo Clinic three sites during the study period, 118 were included. The median age was 62.5 years (IQR:56.0-69.7), and 24.5% were female. The most common mutations in the TTR gene were: Val30Met (n=36, 30.1%), Thr60Ala (n=21, 17.8%), Val122Ile (n=19; 16.1%), others (n=42; 35.6%). Ninety-two patients (78%) were Coutinho FAP stage 1, 24 (20.3%) were stage 2, and 2 were stage 3 (1.7%). Fat aspirate was positive for amyloid in 52/111 patients (46.8%), skin biopsy in 16/33 (48.4%) and nerve biopsy in 19/24 (79.2%) patients. A positive amyloid tissue diagnosis was not associated with mutation, disease severity or duration.

Nerve biopsies are more sensitive than fat aspirate or skin biopsy for amyloid tissue diagnosis in this real-life retrospective cohort of symptomatic, mild ATTRv-PN patients. Fat aspirate and skin biopsy had similar sensitivity and should be considered before nerve biopsy in ATTRv-PN.