Purine nucleoside phosphorylase deficiency

The biosynthesis of purines and pyrimidines is stringently regulated and coordinated by feedback mechanisms that ensure their production in quantities and at times appropriate to varying physiologic demand. Genetic diseases of purine metabolism include gout, Lesch-Nyhan syndrome, adenosine deaminase deficiency, and purine nucleoside phosphorylase deficiency. By contrast, apart from the orotic acidurias, there are few clinically significant disorders of pyrimidine catabolism. 

Adenosine Deaminase Purine Nucleoside Phosphorylase Deficiency... 

Adenosine deaminase deficiency is associated with an immunodeficiency disease in which both thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) are sparse and dysfunctional. Purine nucleoside phosphorylase deficiency is associated with a severe deficiency of T cells but apparently normal B cell function. Immune dysfunctions appear to result from accumulation of dGTP and dATP, which inhibit ribonucleotide reductase and thereby deplete cells of DNA precursors. 

H4. Hershfield, M. S., and Mitchell, B. S., Immunodeficiency diseases caused by adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency. In Metabolic and Molecular Bases of Inherited Disease, 7th ed. (C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, eds.), pp. 1725-1768. McGraw-Hill, New York, 1995. 

In purine nucleoside phosphorylase deficiency, levels of purine nucleotides are high and synthesis of uric acid decreases. High levels of dGTP are apparently responsible for the impairment of T cells that is characteristic of this malady. 

Carson, D.A. Kaye, J. Seegmiller, J.E. Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency possible role of nucleoside kinase(s). Proc. Natl. Acad. Sci. USA, 74, 5677-5681 (1977)... 

In 1975, Giblett and co-workers (18) described a deficiency of the enzyme purine nucleoside phosphorylase in patients with severe combined immunodeficiency disease characterized clinically by a severe abnormality of T-lymphocyte function. ile these patients often exhibit hypouricemia as a result of the deficiency of purine nucleoside phosphorylase, they exhibit at the same time accelerated levels of purine biosynthesis de novo with increased excretion of adenosine, deoxyinosine,guanosine, and deoxyguanosine (19). In addition, the intracellular levels of PRPP are elevated in patients with purine nucleoside phosphorylase deficiency. It is assumed, therefore, that the accelerated rate of purine biosynthesis may be due, at least in part, to the elevated levels of PRPP. It has been suggested that a decreased availability of the substrates hypoxanthine and guanine leads to a decreased functional activity of the enzyme HPRT thus leading to decreased consumption of PRPP and hence the elevated levels observed. 

Simmonds, H.A., Sahota, A., Potter, C.F., Cameron, J.S. Purine metabolism and immunodeficiency urinary purine excretion as a diagnostic screening test in adenosine deaminase and purine nucleoside phosphorylase deficiency. Clin. Sci. and Molec. Med. 54 579-584 (1978). 

J.W.Stoop,B.J.M.Zegers,W.Kuis,C.J.Heijen,J.J.Roord,M.Duran, S.K.Wadman,G.E.J.Staal, Purine Nucleoside Phosphorylase Deficiency Long Term Clinical, Immunological and Metabolic Follow-up. In Primary Immunodeficiencies. Elsevier. Amsterdam 301, (1980). 

A.R.Watson,D.I.K.Evans,H.B.Marsden, V.Miller,P.A.Rogers. Purine nucleoside phosphorylase deficiency associated with a fatal lymphoproliferative disorder. Arch.Dis.ChiId. 

K.C.Rich,E.Mejians,I.H.Fox. Purine nucleoside phosphorylase deficiency improved metabolic and immunological function with erythrocyte transfusion. N.Eng.J.Med.303 973 (1980). 

THE EFFECT OF DEOXYCYTIDINE AND TETRAHYDROURIDINE IN PURINE NUCLEOSIDE PHOSPHORYLASE DEFICIENCY... 

HGPRT hypoxanthine guanine phosphoribosyltransferase deficiency PNP purine nucleoside phosphorylase deficiency... 

J.W. Stoop and S.K. Wadman, Urinary excretion of orotic acid, orotidine and other pyrimidines in a patient with purine nucleoside phosphorylase deficiency, Clin. Chim. Acta, 93 ... 

Table 23.2, Purine nucleoside phosphorylase deficiency [Patients >50 (world)l ...

Pseudo-corpus luteum deficiency Pseudo-neonatal adrenoleukodystrophy Pseudo-vaginal perineoscrotal hypospadia Pseudo-Zellweger syndrome Pterin carbinolamine-4a-dehydratase deficiency Purine nucleoside phosphorylase deficiency Pyroglutamic aciduria... 

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