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.
Al-Saud et al. (2009) described a two-year-old Arab boy born to first cousin parents with purine nucleoside phosphorylase deficiency. He was the eighth child, his two older sisters died from recurrent infections. The first sister died at the age of 3 years without definite diagnosis, while the second sister was diagnosed with PNP deficiency and also died at the age of 3 years. He had two episodes of infections; firstly, a chest infection at the age of 2 months, and secondly, an ear infection at the age of 1 year. He had developmental delays, and he was not able to sit or walk at the age of 1.5 years. Performing sequence analysis for the PNP gene showed a novel homozygous missense mutation (c.487T>C) that resulted in an amino acid substitution (S163P) in the mature PNP enzyme. This substitution lead to a complete loss of PNP function.