Raised IMP-dehydrogenase activity in the erythrocytes of a case of purine nucleoside phosphorylase (PNP) deficiency.

The presenting features of PNP deficiency may be neurological, usually a mild non-progressive spastic diplegia, or related to immunodeficiency which predominantly affects T-lymphocytes. Patients usually die of infection or other manifestations of the immunodeficiency including lymphoma and transfusional graft versus host disease. The disorder may be correctable by bone marrow transplant(1). The lymphotoxicity is probably directly related to the inability to degrade deoxyguanosine with accumulation of dGTP in T-cells. It has been proposed that the neurological deficits may be an indirect consequence of the defect:in the absence of PNP the next step in the purine salvage cycle involving hypoxanthine-guanine phosphoribosyltransferase (HPRT) is unable to operate due to lack of substrate(2). Low erythrocyte GTP levels have been found in PNP deficient subjects, a finding which may reflect a similar inability of the brain (also heavily dependent on a functional salvage cycle) to sustain GTP at levels compatible with normal physiological function(2).This paper reports studies in a PNP deficient individual with spastic diplegia where elevated GTP levels were identified.