Immunodeficiency caused by purine nucleoside phosphorylase deficiency

Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine salvage and degradation pathway. Patients with PNP deficiency typically present with recurrent and unusual infections, autoimmune phenomena, and neurologic abnormalities. The abnormalities in lymphoid and neuronal tissues are believed to be caused by accumulation of deoxyguanosine. Deoxyguanosine accumulation in PNP deficiency leads to its phosphorylation to dGTP, resulting in inhibition of ribonucleotide reductase and DNA synthesis and repair. Inhibition of DNA repair in PNP-deficient thymocytes results in increased thymic apoptosis and abnormal T-cell development.