Purine nucleoside phosphorylase deficiency associated with cellular immunodeficiency: metabolic studies during treatment

Abstract

Until now only a few patients with purine nucleoside phosphorylase (PNP) deficiency have been described and knowledge about quantitative aspects of purine metabolism in this disease is limited^1,2. The data available suggest that PNP deficiency brings about major metabolic disturbances. A massive urinary excretion of inosine, guanosine and the corresponding deoxynucleosides was observed. Presumably these metabolites replace uric acid as the principal end product of purine metabolism as do xanthine and hypoxanthine in xanthine oxidase deficiency. We had the opportunity to study purine excretion in our patient during purine supplement therapy and enzyme replacement with irradiated erythrocytes containing PNP. Daily oral supplements of adenine and hypoxanthine were tried in order to compensate for the lack of purine salvage. Uridine was given at the instigation of American workers, who thought that inosine may induce a secondary adenosine deaminase deficiency state¹, from which pyrimidine starvation may result^3,4. Enzyme replacement therapy was inspired by the success of this approach in a patient with adenosine deaminase deficiency and severe combined immunodeficiency⁵.