Purine Nucleoside Phosphorylase (PNP) Deficiency: A Therapeutic Challenge
Purine nucleoside phosphorylase (PNP:EC 220.127.116.11) deficiency appears to result in a predominantly T cell immune defect1. Lack of the PNP enzyme leads to the inability to degrade deoxynucleosides, particularly deoxyguanosine (dGR) resulting in the intracellular accumulation of deoxyguanosine triphosphate (dGTP) which is known to inhibit DNA synthesis in vitro2. Deoxycytidine kinase is considered responsible for the initial conversion of dGR to dGMP1. Hence deoxycytidine (dCR), the preferred substrate, should competitively inhibit dGTP accumulation as has been demonstrated in vitro1,2. However, oral dCR therapy for six months in a PNP deficient child produced no clinical or immunological improvement, probably due to degradation in the gut or rapid deamination3.
KeywordsHigh Pressure Liquid Chromatography Purine Nucleoside Phosphorylase Amniotic Epithelial Cell Inactivate Polio Vaccine Deoxy Inosine
Unable to display preview. Download preview PDF.
- 1.Enzyme defects and Immunodysfunction. Ciba Symposium 1968 (new series) Amsterdam. Excerpta Medica (1979).Google Scholar
- 3.J.W. Stoop, B.J.M. Zegers, W. Kuis, C.J. Heijen, J.J. Roord, M. Duran, S.K.Wadman,G.E.J.Staal, Purine Nucleoside Phosphorylase Deficiency: Long Term Clinical, Immunological and Metabolic Follow-up. In: Primary Immunodeficiencies. Elsevier. Amsterdam 301, (1980).Google Scholar