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Purine nucleoside phosphorylase deficiency

Author
Eyal Grunebaum, MD
Section Editor
Jennifer M Puck, MD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

Purine nucleoside phosphorylase (PNP) deficiency (MIM #613179) is a rare autosomal recessive immunodeficiency [1-3]. It is characterized by progressive immune abnormalities ranging from severe to nonsevere combined immunodeficiency (table 1) and neurologic symptomatology that includes ataxia, developmental delay, and spasticity. Autoimmunity, especially autoimmune hemolytic anemia, is also frequently present.

This topic reviews the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of PNP deficiency. The related immunodeficiency, adenosine deaminase (ADA) deficiency, is discussed separately. (See "Adenosine deaminase deficiency: Pathogenesis, clinical manifestations, and diagnosis" and "Adenosine deaminase deficiency: Treatment".)

EPIDEMIOLOGY

PNP deficiency constitutes approximately 1 to 2 percent of all combined immunodeficiencies. A literature review in 2011 found 67 patients from 49 families [4], and an update at the end of 2014 reported that there were close to 80 patients [1,5-13]   Subsequently, few additional patients have been described [14,15].

PATHOGENESIS

PNP deficiency is caused by mutations in the PNP gene (MIM #164050) at 14q13.1 (figure 1) [9-13,16-23]. This gene encodes the protein PNP, one of the ubiquitous enzymes involved in the purine salvage pathway [24]. Adenosine deaminase (ADA) deaminates adenosine to yield inosine, which is then converted to hypoxanthine by PNP. PNP also converts guanosine to guanine.

A number of metabolites are elevated in the plasma and urine in PNP deficiency, including deoxyguanosine and deoxyinosine. There is an intracellular accumulation of their deoxy triphosphate compounds, particularly deoxyguanosine triphosphate (dGTP). The latter is toxic to T cells, a property similar to deoxyadenosine triphosphate in ADA deficiency [25-27]. (See "Adenosine deaminase deficiency: Pathogenesis, clinical manifestations, and diagnosis".)

         
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Literature review current through: Sep 2017. | This topic last updated: Sep 29, 2017.
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References
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