Purine nucleoside phosphorylase deficiency

Purine nucleoside phosphorylase deficiency, often called PNP-deficiency, is a rare autosomal recessive metabolic disorder which results in severe combined 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-erythematosis, 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, Pathophysiology and Genetics
The disorder is caused by a mutation of the purine nucleoside phosphorylase (PNP) gene, located at chromosome 14q13.1. PNP is a key enzyme in the purine salvage pathway, and is required for purine degradation. Specifically, it catalyzes the conversion of inosine and guanosine to hypoxanthine. A deficiency of it leads to build up of elevated deoxy-GTP (dGTP) levels resulting in T-cell toxicity and deficiency. In contrast to adenosine deaminase deficiency (another deficiency of purine 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.

Epidemiology
PNP-deficiency is extremely rare. Only 33 patients with the disorder in the United States have been documented. In the United Kingdom only one child has been diagnosed with this disorder.