Abstract
Hereditary transthyretin amyloidosis (ATTRv), the most common form of hereditary amyloidosis, results from autosomal dominant mutations in the TTR gene. Clinical manifestations of ATTRv are typically driven by extracellular amyloid deposition in multiple organs, most notably the peripheral nerves, heart, gastrointestinal tract, and musculoskeletal (MSK) system. We report the case of a 69-year-old man presenting with a two-year history of paresthesias and hypoesthesia in the lower limbs and a complex MSK history, including bilateral carpal tunnel syndrome, multiple trigger finger surgeries, right shoulder arthroplasty, limited left shoulder mobility, and bilateral knee osteoarthritis. Electrophysiological studies revealed mild chronic axonal polyneuropathy. Genetic testing identified a pathogenic heterozygous c.293A>T T78P (p.Tyr98Phe) variant in exon 3 of the TTR gene, confirming a diagnosis of hereditary ATTRv with polyneuropathy (ATTRv-PN). Imaging revealed moderate multilevel spinal spondylosis with severe lumbar stenosis and increased 99m-technetium tracer uptake in major joints, particularly the right knee. Subsequent right knee arthroplasty included synovial tissue sampling, which demonstrated amyloid deposits. This case highlights the MSK manifestations of ATTRv-PN, the role of genetic testing in early diagnosis, and the utility of histopathology in confirming amyloid deposition in surgical specimens.