Recurrent Demyelinating Episodes as Sole Manifestation of Inherited CD59 Deficiency

Abstract

Defects in the regulatory components of the complement system can lead to inflammatory diseases. We present a patient who had four episodes of demyelination in the central nervous system as the only manifestation of inherited CD59 deficiency. Relapsing encephalopathy partially responsive to intravenous immunoglobulin and steroid treatments on the background of parental consanguinity suggested an inherited immune dysregulation. Next generation sequencing revealed homozygous mutation in the CD59 gene, confirmed by lack of CD59 expression on flow cytometry. Inherited CD59 deficiency is a rare autosomal recessive condition characterized by chronic hemolysis, recurrent strokes, and relapsing peripheral demyelinating neuropathy mimicking Guillain–Barré syndrome or chronic inflammatory demyelinating polyneuropathy. Recurrent central nervous system demyelinating episodes as the only manifestation has not been reported to date in inherited CD59 deficiency. This entity should be considered in the differential diagnosis of patients with early-onset recurrent neurological diseases with central or peripheral origin.

Keywords

immune dysregulation - CD59 deficiency - acute disseminated encephalomyelitis - multiphasic disseminated encephalomyelitis

• References

• 1 Yildirim M, Ayvaz DC, Konuskan B. , et al. Neurologic involvement in primary immunodeficiency disorders. J Child Neurol 2018; 33 (05) 320-328
• 2 Haliloglu G, Maluenda J, Sayinbatur B. , et al. Early-onset chronic axonal neuropathy, strokes, and hemolysis: inherited CD59 deficiency. Neurology 2015; 84 (12) 1220-1224
• 3 Ardicli D, Taskiran EZ, Kosukcu C. , et al. Neonatal-onset recurrent Guillain-Barré syndrome-like disease: clues for inherited CD59 deficiency. Neuropediatrics 2017; 48 (06) 477-481
• 4 Al-Mousa H, Al-Dakheel G, Jabr A. , et al. High incidence of severe combined immunodeficiency disease in Saudi Arabia detected through combined t cell receptor excision circle and next generation sequencing of newborn dried blood spots. Front Immunol 2018; 9: 782
• 5 Yuksel D, Oguz KK, Azapagası E. , et al. Uncontrolled inflammation of the nervous system: inherited CD59 deficiency. Neurol Clin Pract 2018; 8 (05) e18-e20
• 6 Atzori M, Battistella PA, Perini P. , et al. Clinical and diagnostic aspects of multiple sclerosis and acute monophasic encephalomyelitis in pediatric patients: a single centre prospective study. Mult Scler 2009; 15 (03) 363-370
• 7 Govender R, Wieselthaler NA, Ndondo A, Wilmshurst JM. Acquired demyelinating disorders of childhood in the Western Cape, South Africa. J Child Neurol 2010; 25 (01) 48-56
• 8 Naidu S, Bibat G, Lin D. , et al. Progressive cavitating leukoencephalopathy: a novel childhood disease. Ann Neurol 2005; 58 (06) 929-938
• 9 Liu M, Zhang J, Zhang Z. , et al. Phenotypic spectrum of mutations in IBA57, a candidate gene for cavitating leukoencephalopathy. Clin Genet 2018; 93 (02) 235-241
• 10 Rubegni A, Ferrari AR, Pasquariello R, Canapicchi R, Santorelli FM, Nesti C. Relapsing-remitting course of cystic leukoencephalopathy. Pediatr Neurol 2018; 89: 63-65
• 11 Karbian N, Eshed-Eisenbach Y, Tabib A. , et al. Molecular pathogenesis of human CD59 deficiency. Neurol Genet 2018; 4 (06) e280
• 12 Harhausen D, Khojasteh U, Stahel PF. , et al. Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice. J Neuroinflammation 2010; 7: 15
• 13 Klemann C, Kirschner J, Ammann S. , et al. CD59 deficiency presenting as polyneuropathy and Moyamoya syndrome with endothelial abnormalities of small brain vessels. Eur J Paediatr Neurol 2018; 22 (05) 870-877
• 14 Ghosh P, Sahoo R, Vaidya A. , et al. A specific and sensitive assay for blood levels of glycated CD59: a novel biomarker for diabetes. Am J Hematol 2013; 88 (08) 670-676
• 15 Höchsmann B, Dohna-Schwake C, Kyrieleis HA, Pannicke U, Schrezenmeier H. Targeted therapy with eculizumab for inherited CD59 deficiency. N Engl J Med 2014; 370 (01) 90-92