Purine nucleoside phosphorylase deficiency

Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited immunodeficiency disorder caused by mutations in the PNP gene located on chromosome 14q13.1. PNP is a key enzyme in the purine salvage pathway, and its deficiency leads to the accumulation of toxic purine metabolites, particularly deoxyguanosine triphosphate (dGTP), which is selectively toxic to T lymphocytes. This results in a progressive and often severe T-cell immunodeficiency, while B-cell function may be relatively preserved initially but can also become impaired over time. The condition is also known as PNP deficiency or immunodeficiency due to purine nucleoside phosphorylase deficiency. The primary body systems affected include the immune system and the nervous system. Patients typically present in infancy or early childhood with recurrent and severe infections, including bacterial, viral, and opportunistic infections. A hallmark feature is progressive lymphopenia with markedly decreased T-cell numbers and function. Approximately two-thirds of affected individuals also develop neurological manifestations, which may include developmental delay, intellectual disability, spasticity, ataxia, and behavioral problems. Autoimmune manifestations, including autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, and lupus-like symptoms, occur in a significant proportion of patients. Some patients may also develop lymphoma or other malignancies. Without treatment, PNP deficiency is often fatal in childhood due to overwhelming infections. The definitive treatment is hematopoietic stem cell transplantation (HSCT), which can restore immune function if performed early. Gene therapy approaches are under investigation. Supportive care includes prophylactic antibiotics, antiviral agents, immunoglobulin replacement therapy, and avoidance of live vaccines. Early diagnosis through newborn screening programs that detect T-cell receptor excision circles (TRECs) or elevated metabolites can facilitate timely intervention and improve outcomes.

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