A 60-year-old man was followed since 2017 for cerebellar ataxia with dysarthria, dysmetria, wide-based gait and hyperreflexia. His initial laboratory evaluation showed normal serum vitamin B12 (404 pg/mL), normal metabolic, autoimmune, and infectious testing, and low ceruloplasmin (16.6 mg/dL) on two occasions. A 24-hour urinary copper excretion was normal (21 µg), and Kayser-Fleischer rings were absent. Genetic testing was declined. Magnetic resonance imaging (MRI) of brain showed cerebellar atrophy. 

He progressed slowly until 2024, when he developed subacute ascending paresthesia with sensory loss to T4, proprioceptive deficits, gait impairment, and cognitive “fog.” Serum vitamin B12 declined to 249 pg/mL and increased to >1200 pg/mL with supplementation. Intrinsic factor–blocking antibodies were positive. Serum copper was low (52 µg/dL) and zinc was decreased (53 µg/dL); both normalized with replacement. ANA increased from 1:80 to 1:5120. MRI of the spine showed progressive posterior column T2 hyperintensity extending along the cord, and brain MRI demonstrated worsening cerebellar atrophy.

CSF analyses showed elevated protein (74–90 mg/dL), matched oligoclonal bands, normal glucose, and no pleocytosis. Infectious, metabolic, autoimmune, and paraneoplastic panels were unrevealing. CSF IL-2 receptor levels were elevated (30.1–33.3 pg/mL). Anti-CD320 antibodies were detected in CSF on a research basis. Treatment with IVIg, steroids, plasmapheresis, cyclophosphamide, and mycophenolate resulted in radiographic stabilization, without clinical improvement.

Anti-CD320–mediated disruption of CNS cobalamin transport should be considered in progressive ataxia and posterior column myelopathy, despite corrected serum B12.