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A rare chronic immune-mediated polyneuropathy characterized by a progressive disabling neuropathy with marked gait disturbance primarily due to sensory ataxia with concurrent cranial neuropathies (internal or external ophthalmoplegia, dysphagia, dysarthria, or facial weakness) and anti-disialosyl IgM antibodies.
ORPHA:71279Classification level: Disorder
- CANDA syndrome
- Chronic ataxic neuropathy-ophthalmoplegia-IgM paraprotein-cold agglutinins-disialosyl antibodies syndrome
- Chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies
- Prevalence: <1 / 1 000 000
- Inheritance: -
- Age of onset: Adult, Elderly
- ICD-10: G61.8
- OMIM: -
- UMLS: C2931684
- MeSH: C537980
- GARD: 9778
- MedDRA: -
The disease is rare with less than 100 cases reported in the literature. The disease predominantly affects males with a ratio of 3:1 (males:females).
The condition appears in adult or elderly age with a median age at onset of 55 years. The clinical picture comprises a chronic neuropathy with marked sensory ataxia and hyporeflexia/areflexia. Patients have relatively preserved motor function in the limbs, although some may develop distal weakness. The clinical manifestations may be fixed, progressive or relapsing-remitting. Electrophysiology and nerve pathology show demyelinating, axonal, or combined demyelinating and axonal features. Nerve ultrasound shows regional nerve enlargement, a finding consistent with acquired demyelination.
The etiology remains incompletely characterized. Evidence suggests direct damage to dorsal root ganglia (DRG) and to the nodal axolemma. It is generally accepted that antibodies against gangliosides are pathogenic. The IgM accounting for the anti-ganglioside activity is almost invariably in the form of an IgM paraprotein, which may also have cold agglutinin activity.
The diagnosis is based on the identification of typical clinical and electrodiagnostic features, IgM antibodies to disialosyl antibodies (i.e. GD1b), cold agglutinins and an IgM monoclonal gammopathy.
Differential diagnosis includes other inflammatory peripheral neuropathies, particularly chronic inflammatory demyelinating polyneuropathy, as well as vascular and demyelinating brainstem lesions.
Management and treatment
Rituximab and/or intravenous immunoglobulin (IVIg) are effective in most patients. IVIg may prevent relapses in responsive patients while rituximab may be most effective in halting disease progression. While there is no clear evidence to support a disease-specific dosing regimen for either agent, commonly utilized regimens for other forms of immune-mediated peripheral nervous system disease have been effective.
The functional outcome is generally guarded-to-poor with the majority of patients suffering some degree of permanent disability from the sensory ataxia that defines the illness.