Purine nucleoside phosphorylase deficiency

Purine nucleoside phosphorylase deficiency is a rare inherited disorder of the immune system. People with it have low numbers of T cells, which recognise and attack invading microbes, and some also have low numbers of B cells, which make antibodies; the most severely affected lack both and have severe combined immunodeficiency. Repeated and persistent infections, mostly of the sinuses and lungs, begin in infancy or early childhood, and organisms that seldom harm healthy people can cause them. Growth is often slower than normal, about two thirds of affected people develop neurological problems such as developmental delay, intellectual disability, poor balance and muscle stiffness, and the risk of autoimmune disorders is raised. Without successful treatment to restore immune function, children usually do not survive past childhood. The cause is mutation in the PNP gene, which makes an enzyme that clears away waste molecules from the breakdown of DNA; when it fails, a substance called deoxyguanosine triphosphate builds up to levels that are toxic to developing T cells. The condition is inherited in an autosomal recessive pattern. Only about 70 affected people had been described in the medical literature, roughly 4 percent of all severe combined immunodeficiency cases.