Neonatal-Onset Recurrent Guillain–Barré Syndrome-Like Disease: Clues for Inherited CD59 Deficiency

Abstract

Inherited CD59 deficiency is a rare autosomal recessive disorder characterized by chronic hemolysis, recurrent ischemic central nervous system strokes, and early-onset relapsing peripheral demyelinating neuropathy mimicking recurrent Guillain–Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP). We report a 7-year-old girl who presented with neonatal-onset relapsing weakness accompanied by diffuse sensory-motor demyelinating peripheral polyneuropathy. She was diagnosed as having a CIDP-like disease and partially responded to immunomodulatory treatments. Cranial magnetic resonance imaging showed multiphasic brainstem and cerebellar ischemic lesions consistent with vasculopathy and chronic left middle cerebral artery infarction. Whole exome sequencing (WES) analysis revealed a frameshift deletion in CD59 (c.146delA, p.Asp49Valfs*31). Inherited CD59 deficiency should be considered in the differential diagnosis of patients with early-onset severe neurologic symptoms even without an overt hemolysis. We would like to highlight the role of WES in the diagnosis of a condition with a targeted therapy.

Recurrent angioedema, Guillain-Barré, and myelitis in a girl with systemic lupus erythematosus and CD59 deficiency syndrome

“…The patient's symptoms were controlled with these medications and the treatment was therefore discontinued. The same onset of our patient's symptoms has also been reported in similar cases [5]. Furthermore, the demyelinating changes in our patient's brain MRI were also observed in other previously reported cases [6].…”

Astrocyte- and neuron-derived extracellular vesicles from Alzheimer’s disease patients effect complement-mediated neurotoxicity

“…Moreover, the MAC endogenous inhibitor CD59 is expressed by neurons (41) and astrocytes (41,42), likely to protect them from uncontrolled neuroinflammation (43,44). CD59 deficiency causes catastrophic neuroinflammatory conditions (45)(46)(47). In AD, protein levels of CD59 and other complement inhibitors are diminished, whereas those of complement effectors increased (44,48), rendering neurons susceptible to complement attack (49).…”

Recurrent Demyelinating Episodes as Sole Manifestation of Inherited CD59 Deficiency

“…Inherited CD59 deficiency is a rare autosomal recessive disorder characterized by chronic subclinical Coombs-negative hemolysis, early-onset recurrent peripheral neuropathy resembling Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP), and recurrent strokes. 2,3 Indeed, we previously described a patient who had been followed-up as CIDP-like disease and multiple CNS infarcts, and a series where three patients from two generations were affected by polyneuropathy and multiple CNS infarcts. 1 Primary involvement of the CNS parenchyma is rare and has been reported in one family from Turkey where two siblings, one with acute disseminated encephalomyelitis (ADEM)-like demyelinating disease in the CNS and the other with subclinical peripheral neuropathy, were diagnosed by whole exome sequencing.…”

“…Inborn errors of immunity can cause neurological diseases affecting the central and peripheral nervous systems: in inherited CD59 deficiency, these have been reported as strokes and peripheral neuropathy. [1][2][3] We present a patient with relapsing central nervous system (CNS) inflammatory disorder diagnosed as inherited CD59 deficiency on his fourth hospital-ization and benefited from fresh frozen plasma (FFP) until eculizumab was started.…”