Neurology. Genetics · 2025
Peripheral Neuropathy in p.Val142Ile (Val122Ile) Variant Hereditary Transthyretin-Mediated Amyloidosis: United Kingdom Experience.
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Zhang Victor Jia Wei, O'Donnell Luke F, Skorupinska Mariola, Carganillo Roy, Rossor Alexander M, Fontana Marianna, Rowczenio Dorota, Gilbertson Janet, Gillmore Julian D, Reilly Mary M
Аннотация
BACKGROUND AND OBJECTIVES: p.Val142Ile (p.V142I) is one of the most common pathogenic transthyretin (TTR) variants typically presents as transthyretin amyloid cardiomyopathy (ATTRv-CM), although frequent concurrent peripheral nerve involvement has been reported (94%). We aimed to characterize the polyneuropathy in p.V142I ATTR amyloidosis (ATTRv-PN) from the UK amyloidosis cohort.
METHODS: We performed a retrospective cohort study of all confirmed p.V142I Variant Transthyretin Amyloidosis (ATTRv) individuals in the National Hospital for Neurology and Neurosurgery Inherited Neuropathy Clinic between January 2019 and October 2024. Because presence of ATTRv-PN was required to access disease-modifying therapy for amyloidosis during this time, all individuals with p.V142I ATTRv were evaluated for neuropathy, providing an unselected cohort.
RESULTS: We identified 52 individuals with p.V142I ATTRv among whom the clinical presentation was cardiac in 47 (90%) and neuropathic in 5 (10%). Age at diagnosis was 71.3 ± 12.2 years. Twenty of the 52 individuals (38%) had symptoms suggestive of neuropathy with an average duration of symptoms of 4.9 ± 3.5 years 20/52 (38%) had signs suggestive of neuropathy with average Neuropathy Impairment Score being 9.0 ± 10.5. After investigations, 21/52 (40%) individuals had clinical features, neurophysiology, and/or skin biopsies consistent with ATTRv-PN (8 large-fiber/13 small-fiber). Six of the 52 individuals (12%) had neuropathies because of alternative etiologies (e.g., diabetes).
DISCUSSION: Real-world experience from the UK national cohort of p.V142I ATTRv indicates that peripheral neuropathy is of a mild severity and less frequent than previously reported.
METHODS: We performed a retrospective cohort study of all confirmed p.V142I Variant Transthyretin Amyloidosis (ATTRv) individuals in the National Hospital for Neurology and Neurosurgery Inherited Neuropathy Clinic between January 2019 and October 2024. Because presence of ATTRv-PN was required to access disease-modifying therapy for amyloidosis during this time, all individuals with p.V142I ATTRv were evaluated for neuropathy, providing an unselected cohort.
RESULTS: We identified 52 individuals with p.V142I ATTRv among whom the clinical presentation was cardiac in 47 (90%) and neuropathic in 5 (10%). Age at diagnosis was 71.3 ± 12.2 years. Twenty of the 52 individuals (38%) had symptoms suggestive of neuropathy with an average duration of symptoms of 4.9 ± 3.5 years 20/52 (38%) had signs suggestive of neuropathy with average Neuropathy Impairment Score being 9.0 ± 10.5. After investigations, 21/52 (40%) individuals had clinical features, neurophysiology, and/or skin biopsies consistent with ATTRv-PN (8 large-fiber/13 small-fiber). Six of the 52 individuals (12%) had neuropathies because of alternative etiologies (e.g., diabetes).
DISCUSSION: Real-world experience from the UK national cohort of p.V142I ATTRv indicates that peripheral neuropathy is of a mild severity and less frequent than previously reported.