The disorder is caused by a mutation of the<unk><unk><unk>  (PNP) 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<unk>  catabolic pathway, and is required for<unk>  degradation. Specifically, it catalyzes the conversion of inosine to hypoxanthine and guanosine to guanine (both guanine and hypoxanthine will be made into xanthine which will then become uric acid). A deficiency of it leads to buildup of elevated deoxy-GTP (dGTP) levels resulting in T-cell toxicity and deficiency. In contrast to adenosine deaminase deficiency (another deficiency of<unk>  metabolism), 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 (chromosome 14 is an autosome), and two copies of the defective gene (one inherited from each parent) 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.
Purine nucleoside phosphorylase deficiency
Dihydropyrimidine dehydrogenase deficiency
Adenine phosphoribosyltransferase deficiency
Dihydrofolate reductase deficiency
Mevalonate kinase deficiency
Guanidinoacetate methyltransferase deficiency
Methylenetetrahydrofolate reductase deficiency
Glutathione synthetase deficiency