CANOMAD mimicking anti-MAG/SGPG neuropathy: A case highlighting the diagnostic specificity of ophthalmoplegia and cold agglutination

Anti-myelin-associated glycoprotein/sulfated glucuronyl paragloboside (MAG/SGPG) neuropathy is a major differential diagnosis for sensory ataxic neuropathy with IgM κ type M proteinemia. Alternatively and less commonly, an important differential diagnosis for chronic sensory ataxic neuropathy with IgM κ type M proteinemia is chronic ataxic neuropathy with ophthalmoplegia, M proteinemia, cold agglutinins, and disialosyl antibodies (CANOMAD), which has been reported to respond to therapies such as intravenous immunoglobulin (IVIg). Confusingly, this case tested positive for anti-SGPG antibodies despite CANOMAD.

A 68-year-old man had sensory ataxia, IgM κ type M protein, prolongation of distal latency without conduction block, and was positive for anti-SGPG IgM antibodies, which could be the misdiagnosis of anti-MAG/SGPG neuropathy. However, the patient had ptosis, binocular diplopia, cold agglutination, and anti-GQ1b IgM antibodies, fulfilling all the key features of CANOMAD. Consistently, IVIg therapy improved both clinical symptoms and electrophysiological findings. After that, anti-MAG antibody testing returned negative results.

Here, we report a case of CANOMAD with the presence of misleading anti-SGPG antibodies, revealing the risk of misdiagnosis because of reliance on anti-SGPG antibodies in the diagnosis of sensory ataxic neuropathy. The present case also emphasized that ocular symptoms (ptosis, binocular diplopia), and cold agglutination were more specific keys to the initial diagnosis of CANOMAD. The accurate diagnosis of CANOMAD may benefit patients by enabling appropriate treatment selection.