Primary CD59 deficiency

Primary CD59 deficiency (also known as CD59 deficiency or hereditary CD59 deficiency) is an extremely rare genetic disorder caused by mutations in the CD59 gene, which encodes a complement regulatory protein (protectin) normally present on the surface of blood cells and other tissues. CD59 functions to prevent the formation of the membrane attack complex (MAC) of the complement system on host cells. When CD59 is absent or nonfunctional, the body's own complement system attacks red blood cells, platelets, and nerve cells, leading to a characteristic triad of clinical features. The hallmark symptoms include complement-mediated hemolytic anemia (chronic destruction of red blood cells resembling paroxysmal nocturnal hemoglobinuria), recurrent thromboembolic events (blood clots), and early-onset relapsing peripheral demyelinating disease resembling chronic inflammatory demyelinating polyneuropathy (CIDP) or Guillain-Barré syndrome. Neurological involvement typically manifests in infancy or early childhood with progressive weakness, hypotonia, and motor developmental delay. The hematological and neurological systems are primarily affected. Treatment with eculizumab, a monoclonal antibody that inhibits terminal complement activation by blocking C5 cleavage, has shown significant benefit in managing both the hemolytic anemia and the neurological manifestations. Early initiation of complement inhibitor therapy may prevent irreversible neurological damage. Supportive care including blood transfusions and physical therapy may also be necessary. Genetic counseling is recommended for affected families.

Common questions about Primary CD59 deficiency