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At a glance

Inherited disease of the purine catabolism. Characterized by severe immunodeficiency, neurological dysfunction, and autoimmunity. Part of the ☞Severe Combined Immune deficiency Syndrome (SCIDS).


Fewer than 100 patients in more than 50 families have been described.

Genetic inheritance

Autosomal recessive.


Purine Nucleoside Phosphorylase Deficiency is caused by mutations in the PNP gene mapped to chromosome 14q13.1. This gene encodes the protein purine nucleoside phosphorylase, one of the enzymes involved in the purine salvage pathway. Purine nucleoside phosphorylase (PNP) is a protein trimer of approximately 90 kDa and present in almost all tissues, but the highest concentration is found in lymphoid tissues. This fact explains why PNP deficiency predominantly affects the lymphatic system. The enzyme is part of the purine salvage pathway and required to catalyze the degradation of (deoxy)inosine and (deoxy)guanosine to hypoxanthine and guanine and, finally, to uric acid. The lack of PNP results in accumulation of deoxyguanosine and deoxyinosine, predominantly in lymphocytes. These two compounds block the enzyme ribonucleotide reductase in T cells, which is used for DNA synthesis (deoxynucleotides), thereby inhibiting the normal T-cell proliferation required for an appropriate immune response. This manifests as defective T-cell immunity and as some degree of B-cell dysfunction.


The combination of neurological defects or recurrent viral infections with undetectable, or extremely low, blood and urine concentrations of uric acid in a child is suggestive of PNP deficiency. In these patients, normally extremely low or even undetectable plasma concentrations of inosine, guanosine, deoxyinosine, and deoxyguanosine are grossly elevated and the same compounds are excreted in excessive amounts in the urine. In severe cases, markedly decreased or even undetectable serum levels of uric acid have been found. The finding of decreased PNP activity in erythrocytes, lymphocytes, or fibroblasts finally confirms the diagnosis. Although heterozygotes show intermediate levels of PNP activity, they appear clinically normal. T-cell function may be normal at birth, but then decreases progressively, although T-cell function may vary to some degree through time. The thymus is significantly reduced in size and histologic examination reveals depletion of thymocytes. In contrast to severe combined immunodeficiency syndrome, Hassall corpuscles in the thymus are present, but they are not well defined. Lymphoid tissue examination shows abnormalities predominantly in T-cell–dependent areas (paracortical zone). Prenatal diagnosis is possible.

Clinical aspects

Generally, neurologic symptoms or recurrent or severe viral (eg, varicella, measles), but also bacterial, fungal (oral candidiasis), mycobacterial, or protozoal infections, with potentially fatal outcome start between the ages of 1 and 5 years. However, symptoms may already occur in the first months of life and include irritability, failure to thrive, hypotonia, lymphopenia, and deficient T-cell–mediated immunity. The B-cell count may be low; however, immunoglobulin levels are often normal, although they may also be ...

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