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 wi th recurrent and unusual infections, autoimmune phenomena, and neurologic a bnormalities. The abnormalities in lymphoid and neuronal tissues are believ ed to be caused by accumulation of deoxyguanosine. Deoxyguanosine accumulat ion in PNP deficiency leads to its phosphorylation to dGTP, resulting in in hibition of ribonucleotide reductase and DNA synthesis and repair. Inhibiti on of DNA repair in PNP-deficient thymocytes results in increased thymic ap optosis and abnormal T-cell development.