Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine salvage pathway with adenosine deaminase (ADA). Inherited deficiency of either one of two purine salvage enzymes results in severe combined immunodeficiency (SCID) in humans.<sup>32 Giblett E.R., Ammann A.J., Wara D.W. , e al. Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity Lancet 1975 ;  1 : 1010  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 33 Giblett E.R., Anderson J.E., Cohen F. , e al. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity Lancet 1972 ;  2 : 1067  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 50 Markert M.L. Purine nucleoside phosphorylase deficiency Immunodefic Rev 1991 ;  3 : 45

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One of the striking features of ADA and PNP deficiencies is the selective effect on the immune system, although the activities of these enzymes are missing in every cell in the body.<sup>50 Markert M.L. Purine nucleoside phosphorylase deficiency Immunodefic Rev 1991 ;  3 : 45

Cliccare qui per andare alla sezione Riferimenti</sup> The biochemical mechanism(s) explaining the pathology of PNP deficiency attempts to address the specificity of this disease toward the immune system.<sup>50 Markert M.L. Purine nucleoside phosphorylase deficiency Immunodefic Rev 1991 ;  3 : 45

Cliccare qui per andare alla sezione Riferimenti, 68 Resta R., Thompson L.F. SCID: The role of adenosine deaminase deficiency Immunol Today 1997 ;  18 : 371

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Enzyme deficiencies can cause deleterious phenotypes as a result of lack of product of the enzymatic reaction or as a consequence of the cytotoxicity of the accumulating substrates. The lack of products in PNP deficiency is unlikely to contribute to the immune deficiency because deficiency of the next enzyme in the purine salvage pathway hypoxanthine-guanine phosphoribosyl transferase (HGPRT) causes Lesch-Nyhan syndrome with normal immune function.<sup>62 Page T., Bakay B., Nissinen E. , e al. Hypoxanthine-guanine phosphoribosyltransferase variants: Correlation of clinical phenotype with enzyme activity J Inher Metab Dis 1981 ;  4 : 203

Cliccare qui per andare alla sezione Riferimenti</sup> Of the four purine nucleoside substrates of the PNP reaction, inosine, deoxyinosine, guanosine, and deoxyguanosine, only deoxyguanosine has an alternative metabolic fate (i.e., phosphorylation by deoxyguanosine kinase) (Figure 1).<sup>28 Eriksson S., Arner E., Spasokoukotskaja T. , e al. Properties and levels of deoxynucleoside kinases in normal and tumor cells: Implications for chemotherapy Adv Enzyme Regul 1994 ;  34 : 13

Cliccare qui per andare alla sezione Riferimenti, 90 Wang L., Hellman U., Eriksson S. Cloning and expression of human mitochondrial deoxyguanosine kinase cDNA FEBS Lett 1996 ;  390 : 39

Cliccare qui per andare alla sezione Riferimenti</sup> Deoxyguanosine is the only logical candidate to mediate the lymphoid abnormalities observed in PNP deficiency. The challenge remains to explain the metabolic, biochemical, and cellular mechanisms that lead to the unique lymphoid specificity of PNP deficiency despite its ubiquitous expression.