To describe a rare case of hereditary transthyretin amyloidosis (hATTR) due to the p.Ile127Val mutation presenting as axonal polyradiculoneuropathy with cranial neuropathies in an African American male.

hATTR is a multisystem disorder caused by pathogenic TTR mutations, leading to amyloid deposition in nerves and organs. Over 130 variants exist, but p.Ile127Val (legacy p.Ile107Val) is among the rarest, previously reported in German, Japanese, and Brazilian populations. Its occurrence in African Americans and clinical presentation mimicking chronic inflammatory demyelinating polyneuropathy (CIDP) is exceedingly uncommon.

We evaluated a 67-year-old African American male with progressive sensorimotor neuropathy, bulbar symptoms, and cranial nerve involvement. Clinical, electrophysiological, imaging, and genetic studies were performed, including EMG/NCS, CSF analysis, technetium pyrophosphate cardiac scintigraphy, PET-CT, MRI brain/spine, and TTR sequencing.

The patient developed length-dependent sensory loss and weakness, bilateral foot drop, dysphagia, and dysarthria over two years. Neurological exam revealed severe sensorimotor deficits, areflexia and cranial neuropathies. EMG/NCS showed diffuse axonal polyradiculoneuropathy with thoracic and cranial denervation. CSF was normal; autoimmune and paraneoplastic panels were negative. PET-CT was unremarkable, while cardiac scintigraphy demonstrated strong uptake consistent with TTR amyloidosis. MRI brain/spine revealed no significant stenosis but showed encephalomalacia of the frontal and left temporal lobes consistent with prior traumatic injury. Genetic testing confirmed a pathogenic heterozygous TTR p.Ile127Val mutation. The clinical phenotype mimicked CIDP, delaying diagnosis. No family history was reported. The patient was initiated on Amvuttra (vutrisiran) therapy.

This case highlights the diagnostic challenge of hATTR presenting as severe polyradiculoneuropathy with cranial involvement. The p.Ile127Val mutation, though rare, should be considered in unexplained axonal neuropathies, even in populations where it is not commonly reported. Early recognition and genetic testing are critical, as disease-modifying therapies such as Amvuttra can significantly alter prognosis.