[PCL-1] Inherited CD59 Deficiency Manifesting as Neonatal-onset Relapsing Axonal Polyneuropathy
Inherited CD59 deficiency is a rare autosomal recessive disorder manifesting in children with severe neurologic symptoms and recurrent hemolytic episodes. A 6-year-old girl presented with neonatal-onset relapsing weakness accompanied by diffuse sensory-motor, demyelinating and axonal peripheral polyneuropathy. She had a relapsing-remitting quadriparesis mimicking recurrent Guillain-Barre syndrome or CIDP, with some improvement after immune modulatory treatments, including steroids, IV immunoglobulins (IVIg), azathioprine and rituximab. Currently, she is wheelchair-bound, with a tracheostomy and gastrostomy tube. She had quadriparesis dominant in the lower extremities with distal atrophy and achilles contractures, absent deep tendon reflexes and severe thoracolumbar scoliosis. She is able to sit without support. Laboratory work-up including metabolic tests were not diagnostic. Cranial MRI showed both supratentorial and infratentorial chronic multifocal ischemic lesions consistent with vasculopathy. Whole exome sequencing (WES) analysis revealed a frame-shift deletion in the CD59 gene (c.146delA, p.Asp49fs). Flow cytometry assay demonstrated the lack of CD59 expression. CD59 is an essential regulatory protein of complement system, which inhibits the final step of the membrane attack complex (MAC) formation and protects cells from complement-mediated lysis. Our patient is on anti-C5 monoclonal antibody (Eculizumab) for 2 months. Inherited CD59 deficiency should be considered in the differential diagnosis of patients with early-onset severe neurologic symptoms (relapsing immune-mediated polyneuropathy and cerebrovascular events) even without an overt hemolysis. We also would like to highlight the role of WES in the diagnosis of a condition with a targeted therapy.