Purine nucleoside phosphorylase deficiency
Purine nucleoside phosphorylase deficiency is a rare autosomal recessive metabolic disorder which results in immunodeficiency.
Signs and symptoms
In addition to the symptoms associated with immunodeficiency, such as depletion of T-cells, decline of lymphocyte activity, and an abrupt proliferation of both benign and opportunistic infections—PNP-deficiency is often characterized by the development of autoimmune disorders. lupus erythematosus, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura have been reported with PNP-deficiency. Neurological symptoms, such as developmental decline, hypotonia, and mental retardation have also been reported.Cause
The disorder is caused by a mutation of the purine nucleoside phosphorylase gene, located at chromosome 14q13.1. This mutation was first identified by Eloise Giblett, a professor at the University of Washington, in 1975. PNP is a key enzyme in the purine catabolic pathway, and is required for purine degradation. Specifically, it catalyzes the conversion of inosine to hypoxanthine and guanosine to guanine. A deficiency of it leads to a buildup of elevated deoxy-GTP levels resulting in T-cell toxicity and deficiency. In contrast to adenosine deaminase deficiency, there is minimal disruption to B cells.PNP deficiency is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.