Purine nucleoside phosphorylase deficiency is a rare severe combined immunodeficiency disorder, characterized by profound T cell deficiency, recurrent and opportunistic infections, progressive neurologic manifestations, autoimmunity disorders and malignancy.  The neurologic symptoms include: spasticity, ataxia, developmental delay, or intellectual disability.  To date, about 70 cases have been identified with purine nucleoside phosphorylase deficiency.  Diagnosis is based on clinical symptoms, and the results of laboratory testing showing leucopenia, severe lymphopenia, and neutropenia.  Treatment with hematopoietic stem cell transplantation (HSCT) is the only option for the immune deficiency, but it does not improve the neurologic symptoms.  If left untreated, affected children usually do not survive past the first decade of life. 

Loss-of-function mutations in the PNP gene, located on chromosome 14q11.2, have been identified in patients with purine nucleoside phosphorylase deficiency.  This gene encodes a key enzyme in the purine salvage pathway.