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 I...

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Main Authors: Homare Funasaka, Akira Hanazono, Koh Abe, Takaya Yamashita, Hinako Shimada, Keita Yasuda, Yoshiko Takahashi, Yui Sanpei, Masashiro Sugawara
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:eNeurologicalSci
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405650225000346
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author Homare Funasaka
Akira Hanazono
Koh Abe
Takaya Yamashita
Hinako Shimada
Keita Yasuda
Yoshiko Takahashi
Yui Sanpei
Masashiro Sugawara
author_facet Homare Funasaka
Akira Hanazono
Koh Abe
Takaya Yamashita
Hinako Shimada
Keita Yasuda
Yoshiko Takahashi
Yui Sanpei
Masashiro Sugawara
author_sort Homare Funasaka
collection DOAJ
description 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.
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spelling doaj-art-8be65cbc589c4167b4127dcdfe9de47b2025-08-20T03:58:00ZengElseviereNeurologicalSci2405-65022025-09-014010058010.1016/j.ensci.2025.100580CANOMAD mimicking anti-MAG/SGPG neuropathy: A case highlighting the diagnostic specificity of ophthalmoplegia and cold agglutinationHomare Funasaka0Akira Hanazono1Koh Abe2Takaya Yamashita3Hinako Shimada4Keita Yasuda5Yoshiko Takahashi6Yui Sanpei7Masashiro Sugawara8Omagari Kosei Medical Center, Department of Neurology, Japan; Akita University Graduate School of Medicine, Department of Neurology, Japan; Corresponding author at: 8-65 Omagari Torimachi, Daisen, Akita, Japan.Akita University Graduate School of Medicine, Department of Neurology, JapanAkita University Graduate School of Medicine, Department of Hematology, Nephrology and Rheumatology, JapanAkita University Graduate School of Medicine, Department of Hematology, Nephrology and Rheumatology, JapanAkita University Graduate School of Medicine, Department of Neurology, JapanAkita University Graduate School of Medicine, Department of Neurology, JapanAkita University Graduate School of Medicine, Department of Neurology, JapanAkita University Graduate School of Medicine, Department of Neurology, JapanAkita University Graduate School of Medicine, Department of Neurology, JapanAnti-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.http://www.sciencedirect.com/science/article/pii/S2405650225000346CANOMADSensory ataxic neuropathyAnti-myelin-associated glycoproteinAnti-sulfated glucuronyl paraglobosideOphthalmoplegiaParaproteinemia
spellingShingle Homare Funasaka
Akira Hanazono
Koh Abe
Takaya Yamashita
Hinako Shimada
Keita Yasuda
Yoshiko Takahashi
Yui Sanpei
Masashiro Sugawara
CANOMAD mimicking anti-MAG/SGPG neuropathy: A case highlighting the diagnostic specificity of ophthalmoplegia and cold agglutination
eNeurologicalSci
CANOMAD
Sensory ataxic neuropathy
Anti-myelin-associated glycoprotein
Anti-sulfated glucuronyl paragloboside
Ophthalmoplegia
Paraproteinemia
title CANOMAD mimicking anti-MAG/SGPG neuropathy: A case highlighting the diagnostic specificity of ophthalmoplegia and cold agglutination
title_full CANOMAD mimicking anti-MAG/SGPG neuropathy: A case highlighting the diagnostic specificity of ophthalmoplegia and cold agglutination
title_fullStr CANOMAD mimicking anti-MAG/SGPG neuropathy: A case highlighting the diagnostic specificity of ophthalmoplegia and cold agglutination
title_full_unstemmed CANOMAD mimicking anti-MAG/SGPG neuropathy: A case highlighting the diagnostic specificity of ophthalmoplegia and cold agglutination
title_short CANOMAD mimicking anti-MAG/SGPG neuropathy: A case highlighting the diagnostic specificity of ophthalmoplegia and cold agglutination
title_sort canomad mimicking anti mag sgpg neuropathy a case highlighting the diagnostic specificity of ophthalmoplegia and cold agglutination
topic CANOMAD
Sensory ataxic neuropathy
Anti-myelin-associated glycoprotein
Anti-sulfated glucuronyl paragloboside
Ophthalmoplegia
Paraproteinemia
url http://www.sciencedirect.com/science/article/pii/S2405650225000346
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