Amyloid neuropathy, caused by insoluble amyloid deposits in the peripheral nervous system, primarily occurs in light-chain amyloidosis (AL) and hereditary transthyretin amyloidosis (ATTRv). AL is due to abnormal plasma cell activity, while ATTRv results from TTR gene mutations. These deposits disrupt nerve function, leading to sensory and autonomic symptoms. Diagnosis involves nerve conduction studies, sudomotor axon testing, and tissue biopsies. Treatments like monoclonal antibodies and gene therapies are improving survival and quality of life. Early diagnosis and presymptomatic testing for ATTRv are crucial.

AL amyloidosis affects 8 to 12 people per million annually in the US, mainly impacting the heart and kidneys, with many patients also developing neuropathy. Despite treatment advancements, delayed diagnosis remains a challenge. ATTRv amyloidosis is most common in Portugal, Sweden, Brazil, and Japan, with peripheral neuropathy as the main symptom. New therapies like TTR stabilizers and gene silencers have largely replaced liver transplantation. Diagnosis requires clinical evaluation, genetic testing, and tissue biopsy, with newer imaging techniques aiding detection. Early and accurate diagnosis is vital to prevent long-term disability and improve outcomes.

Reference: Chompoopong P, Mauermann ML, Siddiqi H, Peltier A. Amyloid Neuropathy: From Pathophysiology to Treatment in Light-Chain Amyloidosis and Hereditary Transthyretin Amyloidosis. Ann Neurol. 2024 Jun 24. doi: 10.1002/ana.26965. Epub ahead of print. PMID: 38923548.