Purine nucleoside phosphorylase deficiency

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Purine nucleoside phosphorylase deficiency
Autosomal recessive - en.svg
Purine nucleoside phosphorylase deficiency has an autosomal recessive pattern of inheritance
Classification and external resources
ICD-10 D81.5
ICD-9-CM 277.2
OMIM 613179
DiseasesDB 11044
eMedicine ped/1957
Orphanet 760

Purine nucleoside phosphorylase deficiency, often called PNP-deficiency, is a rare autosomal recessive[1] metabolic disorder which results in immunodeficiency.

Signs and symptoms[edit]

In addition to the symptoms associated with immunodeficiency, such as depletion of T-cells, decline of lymphocyte activity, and an abrupt proliferation of both benign and opportunistic infections — PNP-deficiency is often characterized by the development of autoimmune disorders. lupus erythematosus, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura have been reported with PNP-deficiency.[2]

Neurological symptoms, such as developmental decline, hypotonia, and mental retardation have also been reported.


The disorder is caused by a mutation of the purine nucleoside phosphorylase (PNP) gene, located at chromosome 14q13.1.[3][4] PNP is a key enzyme in the purine salvage pathway, and is required for purine degradation. Specifically, it catalyzes the conversion of inosine to hypoxanthine and guanosine to guanine (both guanine and hypoxanthine will be made into xanthine which will then become uric acid). A deficiency of it leads to buildup of elevated deoxy-GTP (dGTP) levels resulting in T-cell toxicity and deficiency.[4][5] In contrast to adenosine deaminase deficiency (another deficiency of purine metabolism), there is minimal disruption to B cells.[6]

PNP deficiency is inherited in an autosomal recessive manner.[1] This means the defective gene responsible for the disorder is located on an autosome (chromosome 14 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.




PNP-deficiency is extremely rare. Only 33 patients with the disorder in the United States have been documented.[2] In the United Kingdom only one child has been diagnosed with this disorder.[7]

See also[edit]


  1. ^ a b Sasaki Y, Iseki M, Yamaguchi S, Kurosawa Y, Yamamoto T, Moriwaki Y, Kenri T, Sasaki T, Yamashita R (July 1998). "Direct evidence of autosomal recessive inheritance of Arg24 to termination codon in purine nucleoside phosphorylase gene in a family with a severe combined immunodeficiency patient". Human Genetics. 103 (1): 81–85. PMID 9737781. doi:10.1007/s004390050787. 
  2. ^ a b Markert ML (1991). "Purine nucleoside phosphorylase deficiency". Immunodefic Rev. 3 (1): 45–81. PMID 1931007. 
  3. ^ Online Mendelian Inheritance in Man (OMIM) 164050
  4. ^ a b Snyder FF, Jenuth JP, Mably ER, Mangat RK (Mar 1997). "Point mutations at the purine nucleoside phosphorylase locus impair thymocyte differentiation in the mouse" (Free full text). Proc. Natl. Acad. Sci. U.S.A. 94 (6): 2522–2527. PMC 20121Freely accessible. PMID 9122228. doi:10.1073/pnas.94.6.2522. 
  5. ^ Toro A, Grunebaum E (Oct 2006). "TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice" (Free full text). J. Clin. Invest. 116 (10): 2717–2726. PMC 1560347Freely accessible. PMID 16964310. doi:10.1172/JCI25052. 
  6. ^ "eMedicine - Purine Nucleoside Phosphorylase Deficiency : Article by Alan P Knutsen". Retrieved July 25, 2010. 
  7. ^ http://www.channel4.com/news/articles/society/health/boy+first+in+uk+with+rare+condition/3022087