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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Purine nucleoside phosphorylase deficiency

Reviewed April 2012

What is purine nucleoside phosphorylase deficiency?

Purine nucleoside phosphorylase deficiency is one of several disorders that damage the immune system and cause severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from foreign invaders such as bacteria, viruses, and fungi. Affected individuals are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. Infants with SCID typically grow much more slowly than healthy children and experience pneumonia, chronic diarrhea, and widespread skin rashes. Without successful treatment to restore immune function, children with SCID usually do not survive past early childhood.

About two-thirds of individuals with purine nucleoside phosphorylase deficiency have neurological problems, which may include developmental delay, intellectual disability, difficulties with balance and coordination (ataxia), and muscle stiffness (spasticity). People with purine nucleoside phosphorylase deficiency are also at increased risk of developing autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs.

How common is purine nucleoside phosphorylase deficiency?

Purine nucleoside phosphorylase deficiency is rare; only about 70 affected individuals have been identified. This disorder accounts for approximately 4 percent of all SCID cases.

What genes are related to purine nucleoside phosphorylase deficiency?

Purine nucleoside phosphorylase deficiency is caused by mutations in the PNP gene. The PNP gene provides instructions for making an enzyme called purine nucleoside phosphorylase. This enzyme is found throughout the body but is most active in specialized white blood cells called lymphocytes. These cells protect the body against potentially harmful invaders by making immune proteins called antibodies that tag foreign particles and germs for destruction or by directly attacking virus-infected cells. Lymphocytes are produced in specialized lymphoid tissues including the thymus and lymph nodes and then released into the blood. The thymus is a gland located behind the breastbone; lymph nodes are found throughout the body. Lymphocytes in the blood and in lymphoid tissues make up the immune system.

Purine nucleoside phosphorylase is known as a housekeeping enzyme because it clears away waste molecules that are generated when DNA is broken down. Mutations in the PNP gene reduce or eliminate the activity of purine nucleoside phosphorylase. The resulting excess of waste molecules and further reactions involving them lead to the buildup of a substance called deoxyguanosine triphosphate (dGTP) to levels that are toxic to lymphocytes. Immature lymphocytes in the thymus are particularly vulnerable to a toxic buildup of dGTP, which damages them and triggers their self-destruction (apoptosis). The number of lymphocytes in other lymphoid tissues is also greatly reduced, resulting in the immune deficiency characteristic of purine nucleoside phosphorylase deficiency.

Related Gene(s)

Changes in this gene are associated with purine nucleoside phosphorylase deficiency.

  • PNP

How do people inherit purine nucleoside phosphorylase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of purine nucleoside phosphorylase deficiency?

These resources address the diagnosis or management of purine nucleoside phosphorylase deficiency and may include treatment providers.

  • Baby's First Test: Severe Combined Immunodeficiency (
  • Genetic Testing Registry: Purine-nucleoside phosphorylase deficiency (
  • National Marrow Donor Program (

You might also find information on the diagnosis or management of purine nucleoside phosphorylase deficiency in Educational resources and Patient support.

General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing (, particularly the difference between clinical tests and research tests (

To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook.

Where can I find additional information about purine nucleoside phosphorylase deficiency?

You may find the following resources about purine nucleoside phosphorylase deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for purine nucleoside phosphorylase deficiency?

  • nucleoside phosphorylase deficiency
  • PNP deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about purine nucleoside phosphorylase deficiency?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding purine nucleoside phosphorylase deficiency?

apoptosis ; ataxia ; autoimmune ; autosomal ; autosomal recessive ; bacteria ; cell ; chronic ; deficiency ; developmental delay ; disability ; DNA ; enzyme ; gene ; immune system ; immunodeficiency ; inherited ; lymph ; lymphoid ; neurological ; nucleoside ; pneumonia ; recessive ; spasticity ; thymus ; toxic ; virus ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Alangari A, Al-Harbi A, Al-Ghonaium A, Santisteban I, Hershfield M. Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients. Ann Saudi Med. 2009 Jul-Aug;29(4):309-12. (
  • Al-Saud B, Alsmadi O, Al-Muhsen S, Al-Ghonaium A, Al-Dhekri H, Arnaout R, Hershfield MS, Al-Mousa H. A novel mutation in purine nucleoside phosphorylase in a child with normal uric acid levels. Clin Biochem. 2009 Nov;42(16-17):1725-7. doi: 10.1016/j.clinbiochem.2009.08.017. Epub 2009 Sep 3. (
  • Aytekin C, Dogu F, Tanir G, Guloglu D, Santisteban I, Hershfield MS, Ikinciogullari A. Purine nucleoside phosphorylase deficiency with fatal course in two sisters. Eur J Pediatr. 2010 Mar;169(3):311-4. doi: 10.1007/s00431-009-1029-6. Epub 2009 Aug 6. (
  • Grunebaum E, Zhang J, Roifman CM. Novel mutations and hot-spots in patients with purine nucleoside phosphorylase deficiency. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1411-5. Erratum in: Nucleosides Nucleotides Nucleic Acids. 2005;24(4):303. (
  • Nyhan WL. Disorders of purine and pyrimidine metabolism. Mol Genet Metab. 2005 Sep-Oct;86(1-2):25-33. Review. (
  • Ozkinay F, Pehlivan S, Onay H, van den Berg P, Vardar F, Koturoglu G, Aksu G, Unal D, Tekgul H, Can S, Ozkinay C. Purine nucleoside phosphorylase deficiency in a patient with spastic paraplegia and recurrent infections. J Child Neurol. 2007 Jun;22(6):741-3. (
  • Walker PL, Corrigan A, Arenas M, Escuredo E, Fairbanks L, Marinaki A. Purine nucleoside phosphorylase deficiency: a mutation update. Nucleosides Nucleotides Nucleic Acids. 2011 Dec;30(12):1243-7. doi: 10.1080/15257770.2011.630852. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: April 2012
Published: February 8, 2016