Severe sensory ataxia and demyelinating polyneuropathy with IgM anti-GM2 and GalNAc-GD1A antibodies.
Several polyneuropathy syndromes have been described with polyclonal serum immunoglobulin G (IgG) or immunoglobulin M (IgM) binding to gangliosides GM2 and GalNAc-GD1a that contain the terminal trisaccharide moiety GalNAc(beta1-4)Gal(alpha2-3)NeuAc. We describe the clinical and electrodiagnostic features in two patients with serum IgM monoclonal anti-GM2 and anti-GalNAc-GD1a antibodies. These patients had slowly progressive, panmodal sensory loss with severe sensory ataxia. Electrodiagnostic testing showed demyelinating features. Prominent improvement in gait ataxia occurred after treatment with human immune globulin but not after other immunomodulating therapies. Enzyme-linked immunoabsorbent assay and thin-layer chromatography demonstrate that the patient's serum monoclonal IgM bound to gangliosides GM2 and GalNac-GD1a but not to gangliosides without the GalNAc(beta1-4)Gal(alpha2-3)NeuAc moiety. This neuropathy differs from previously reported neuropathy syndromes associated with polyclonal GM2 and GalNAc-GD1a antibodies and from other chronic demyelinating polyneuropathies. We conclude that a distinct syndrome of chronic demyelinating neuropathy with sensory ataxia, unresponsive to corticosteroids, is associated with monoclonal IgM binding to gangliosides with a terminal GalNAc(beta1-4)Gal(alpha2-3)NeuAc trisaccharide moiety. Diagnosis of this syndrome is important to direct appropriate treatment.
Department of Neurology, Box 8111, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, Missouri 63110, USA. lopateg@neuro.wustl.edu
Glenn
G
Lopate
Rati
R
Choksi
Alan
A
Pestronk
D001259:Ataxia / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D002855:Chromatography, Thin Layer; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D004568:Electrodiagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005678:G(M2) Ganglioside / Q000276:immunology*; D020233:Gait Disorders, Neurologic / Q000209:etiology; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011115:Polyneuropathies / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology
D005732:Gangliosides; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D005678:G(M2) Ganglioside; C055253:IV(4)-galactosyl-N-acetylganglioside GD1a