Purine nucleoside phosphorylase deficiency

A rare genetic disorder affecting the immune system

Purine nucleoside phosphorylase deficiency (PNP deficiency) is a rare genetic disorder that affects the immune system. It is classified as a type of primary immunodeficiency and is caused by mutations in the PNP gene. This condition leads to the accumulation of toxic metabolites, which primarily affect T cells, a type of white blood cell crucial for the immune response.

Pathophysiology

Purine nucleoside phosphorylase is an enzyme involved in the purine salvage pathway, which is essential for the breakdown and recycling of purines, the building blocks of DNA and RNA. In individuals with PNP deficiency, the enzyme is either absent or non-functional, leading to the accumulation of deoxyguanosine and other toxic metabolites. These substances are particularly harmful to lymphocytes, especially T lymphocytes, resulting in lymphopenia and impaired immune function.

Clinical Features

Patients with PNP deficiency typically present with recurrent infections due to the compromised immune system. Common infections include those caused by bacteria, viruses, and fungi. In addition to immunodeficiency, affected individuals may exhibit neurological symptoms such as developmental delay, ataxia, and spasticity. Autoimmune disorders, such as autoimmune hemolytic anemia and autoimmune thrombocytopenia, may also occur.

Diagnosis

The diagnosis of PNP deficiency is based on clinical evaluation, laboratory tests, and genetic analysis. Laboratory findings often reveal low levels of T cells and elevated levels of toxic metabolites in the blood. Genetic testing can confirm mutations in the PNP gene, providing a definitive diagnosis.

Treatment

Management of PNP deficiency involves supportive care and measures to prevent infections. Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment, as it can restore normal immune function. Prior to transplantation, patients may receive immunoglobulin replacement therapy and antibiotic prophylaxis to reduce the risk of infections.

Prognosis

The prognosis for individuals with PNP deficiency varies depending on the severity of the condition and the success of treatment. Early diagnosis and intervention, particularly with HSCT, can significantly improve outcomes. Without treatment, the condition can be life-threatening due to severe infections and complications.

Related pages

• Primary immunodeficiency
• Hematopoietic stem cell transplantation
• Autoimmune disease
• Lymphocyte