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Purine nucleoside phosphorylase deficiency

Arye Rubinstein, MD
Section Editor
Jennifer M Puck, MD
Deputy Editor
Elizabeth TePas, MD, MS


Purine nucleoside phosphorylase (PNP) deficiency (MIM #613179) is a rare autosomal recessive immunodeficiency. It is characterized by a progressive combined immunodeficiency (table 1) and neurologic symptomatology that includes ataxia, developmental delay, and spasticity. Autoimmunity, especially autoimmune hemolytic anemia, is also frequently present.

The disease was first described in 1975 in a patient who had absent T cell function but intact B cell immunity [1]. The immunodeficiency was progressive, with normal immune functions at birth, but severe T cell deficiency with intact B cells exhibited by the age of two years [2]. A complete absence of PNP was noted in red blood cells, white blood cells, and fibroblasts [1]. It was subsequently reported that the parents of this patient had approximately one-half of the normal levels of PNP, indicating an autosomal recessive inheritance [3].

This topic discusses 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".)


PNP deficiency constitutes approximately 1 to 2 percent of all combined immunodeficiencies. It has been reported in less than 50 patients from 30 families [1,4-11].


PNP deficiency is caused by mutations in the PNP gene (MIM #164050) at 14q13.1 (figure 1) [7-19]. This gene encodes the protein PNP, one of the enzymes involved in the purine salvage pathway [20]. Adenosine deaminase (ADA) deaminates adenosine to yield inosine, which is then converted to hypoxanthine by PNP. PNP also converts guanosine to guanine.


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Literature review current through: Sep 2016. | This topic last updated: Feb 24, 2016.
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