Cobalamin Transporter Antibody-associated Ataxia and Longitudinal Posterior Column Myelopathy: A Diagnostic Challenge
Kaila Anderson1, Laura Grezzo1, John Pluvinage3, Michael Wilson3, Sarah Berman4, Cigdem Isitan-Alkawadri2, Jenny Linnoila2
1Neurology, University of Pittsburgh Medical Center, 2University of Pittsburgh Medical Center, 3University of California San Francisco, 4University of Pittsburgh
Objective:
To describe a progressive cerebellar and spinal cord syndrome associated with anti-CD320 antibodies in a patient with initially normal serum vitamin B12 and nondiagnostic evaluation.
Background:
Progressive cerebellar ataxia with posterior column myelopathy has a broad differential, including nutritional, metabolic, autoimmune, and neurodegenerative etiologies. Antibodies to CD320, the transcobalamin II receptor required for cellular cobalamin uptake, have recently been implicated in immune-mediated neurologic dysfunction.
Design/Methods:
Not applicable.
Results:

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.

Conclusions:

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

10.1212/WNL.0000000000217670
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