Chronic Hemolysis, Steroid-Dependent CIDP, and Progressive Moya-Moya Disease Due to Hereditary Immune Dysregulation

Case Report: The first son of healthy consanguineous Turkish parents presented at the age of 14 months with coombs-negative hemolytic anemia and acute Guillain-Barré syndrome. At the age of 27 months, repeated relapses gave rise to the diagnosis of CIDP. During the following years, this responded well to treatment with corticosteroids, but immunoglobulins and various immunosuppressants were without convincing effect. At the age of 6 years for the first time signs of cerebral ischemia appeared. We detected stenosing vasculitis of multiple large cerebral arteries to be causative. During the following 2 years, these showed severe progression despite aggressive treatment. Systemic vasculitic diseases and immune defects were excluded repeatedly. Chronic hemolysis, steroid-dependent Eventually, this progression resulted in secondary Moya-Moya disease and the boy died at the age of 8 years due to multiple malignant cerebral infractions. Only 4 years later following recent publications in the literature, we identified a homozygous mutation in the CD59 gene to be causative. CD59 is an inhibitor of the membrane-attack complex at the end of the complement pathway. Acquired CD59 deficiency has since long been known as the cause of paroxysmal nocturnal hemoglobinuria (PNH). Families with inherited CD59 defects presenting with the same signs as our patients have first been reported in 2013. Treatment with eculizumab has been reported to be effective in PNH and in one of these cases.

Conclusion: In children with this unusual combination of findings, a CD59 mutation should be considered early. Treatment with eculizumab could be considered as effective.