Purine nucleoside phosphorylase deficiency: Difference between revisions

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{{Infobox medical condition (new)
{{SI}}
{{Infobox medical condition
| name            = Purine nucleoside phosphorylase deficiency
| name            = Purine nucleoside phosphorylase deficiency
| image          = Autosomal recessive - en.svg
| image          = [[File:Autosomal_recessive_-_en.svg|200px]]
| caption        = Purine nucleoside phosphorylase deficiency has an autosomal recessive pattern of inheritance
| caption        = Purine nucleoside phosphorylase deficiency is inherited in an [[autosomal recessive]] pattern.
| synonyms       = '''PNP-deficiency'''
| synonyms       = PNP deficiency
| complications  =  
| field          = [[Immunology]], [[Genetics]]
| onset          =  
| symptoms        = [[Immunodeficiency]], [[neurological disorders]], [[autoimmune disorders]]
| duration        =  
| complications  = [[Infections]], [[neurological impairment]]
| types          =
| onset          = [[Infancy]] or [[early childhood]]
| causes          =  
| duration        = [[Chronic]]
| risks          =  
| causes          = Mutations in the [[PNP gene]]
| diagnosis      =  
| risks          = [[Consanguinity]]
| differential    =  
| diagnosis      = [[Genetic testing]], [[enzyme assay]]
| prevention      =  
| differential    = [[Severe combined immunodeficiency]], [[Adenosine deaminase deficiency]]
| treatment      = Allegeneic hemotopoietic stem cell transplantation (HSCT)
| prevention      = [[Genetic counseling]]
| medication      =
| treatment      = [[Hematopoietic stem cell transplantation]], [[enzyme replacement therapy]]
| prognosis      =  
| prognosis      = Variable, depends on treatment
| frequency      =  
| frequency      = Rare
| deaths          =
}}
}}
 
{{Short description|A rare genetic disorder affecting the immune system}}
'''Purine nucleoside phosphorylase deficiency''', is a rare [[autosome|autosomal]] [[dominance (genetics)|recessive]]<ref name=pnpar>{{Cite journal| doi = 10.1007/s004390050787|vauthors=Sasaki Y, Iseki M, Yamaguchi S, Kurosawa Y, Yamamoto T, Moriwaki Y, Kenri T, Sasaki T, Yamashita R | title = 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| journal = Human Genetics| volume = 103| issue = 1| pages = 81&ndash;85| date = July 1998| pmid = 9737781}}</ref> [[inborn errors of metabolism|metabolic disorder]] which results in [[immunodeficiency]].
'''Purine nucleoside phosphorylase deficiency''' (PNP deficiency) is a rare [[genetic disorder]] that affects the [[immune system]]. It is classified as a type of [[primary immunodeficiency]] and is caused by mutations in the [[PNP gene]]. This condition leads to the accumulation of toxic metabolites, which primarily affect [[T cells]], a type of [[white blood cell]] crucial for the immune response.
 
==Pathophysiology==
==Signs and symptoms==
Purine nucleoside phosphorylase is an enzyme involved in the [[purine salvage pathway]], which is essential for the breakdown and recycling of purines, the building blocks of [[DNA]] and [[RNA]]. In individuals with PNP deficiency, the enzyme is either absent or non-functional, leading to the accumulation of deoxyguanosine and other toxic metabolites. These substances are particularly harmful to [[lymphocytes]], especially [[T lymphocytes]], resulting in [[lymphopenia]] and impaired immune function.
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 &mdash; PNP-deficiency is often characterized by the development of [[autoimmune disorder]]s. [[lupus erythematosus]], autoimmune [[hemolytic anemia]], and [[idiopathic thrombocytopenic purpura]] have been reported with PNP-deficiency.<ref name="pnpone">{{cite journal |author=Markert ML |title=Purine nucleoside phosphorylase deficiency |journal=Immunodefic Rev. |volume=3 |issue=1 |pages=45–81 |year=1991 |pmid=1931007 }}</ref>
==Clinical Features==
 
Patients with PNP deficiency typically present with recurrent infections due to the compromised immune system. Common infections include those caused by [[bacteria]], [[viruses]], and [[fungi]]. In addition to immunodeficiency, affected individuals may exhibit [[neurological symptoms]] such as developmental delay, [[ataxia]], and [[spasticity]]. Autoimmune disorders, such as [[autoimmune hemolytic anemia]] and [[autoimmune thrombocytopenia]], may also occur.
Neurological symptoms, such as developmental decline, [[hypotonia]], and [[mental retardation]] have also been reported.
 
==Cause==
The disorder is caused by a mutation of the [[purine nucleoside phosphorylase]] (PNP) gene, located at [[chromosome]] [[chromosome 14 (human)|14q13.1]].<ref>{{OMIM|164050}}</ref><ref name="pmid9122228"/> This mutation was first identified by [[Eloise Giblett]], a professor at the [[University of Washington]], in 1975.<ref>Motulsky A, Gartler S. "Biographical Memoirs: Eloise R. Giblett". ''National Academy of Sciences''.</ref> PNP is a key [[enzyme]] in the purine catabolic<ref>{{cite book|last1=Berg|first1=Jeremy M.|last2=Tymoczko|first2=John L.|last3=Stryer|first3=Lubert|title=Biochemistry|isbn=9781429229364|page=753|edition=7th|date=2010-12-24}}</ref> 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.<ref name="pmid9122228">{{cite journal |vauthors=Snyder FF, Jenuth JP, Mably ER, Mangat RK |title=Point mutations at the purine nucleoside phosphorylase locus impair thymocyte differentiation in the mouse |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue=6 |pages=2522&ndash;2527 |date=Mar 1997 |pmid=9122228 |pmc=20121 |doi= 10.1073/pnas.94.6.2522|bibcode=1997PNAS...94.2522S }}</ref><ref name="pmid16964310">{{cite journal |vauthors=Toro A, Grunebaum E |title=TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice |journal=J. Clin. Invest. |volume=116 |issue=10 |pages=2717&ndash;2726 |date=Oct 2006 |pmid=16964310 |pmc=1560347 |doi=10.1172/JCI25052}}</ref> In contrast to [[adenosine deaminase deficiency]] (another deficiency of [[purine metabolism]]), there is minimal disruption to [[B cell]]s.<ref name="urleMedicine - Purine Nucleoside Phosphorylase Deficiency : Article by Alan P Knutsen">{{cite web |url=http://www.emedicine.com/ped/TOPIC1957.HTM |title=eMedicine - Purine Nucleoside Phosphorylase Deficiency : Article by Alan P Knutsen |accessdate=July 25, 2010 }}</ref>
 
PNP deficiency is inherited in an autosomal recessive manner.<ref name=pnpar/> 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 [[genetic carrier|carry]] one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
 
==Diagnosis==
==Diagnosis==
Diagnostic methods
The diagnosis of PNP deficiency is based on clinical evaluation, laboratory tests, and genetic analysis. Laboratory findings often reveal low levels of T cells and elevated levels of toxic metabolites in the blood. Genetic testing can confirm mutations in the PNP gene, providing a definitive diagnosis.
 
Diagnosis is based on the clinical examination and on laboratory findings showing leukopenia, severe lymphopenia with low CD3, CD4, and CD8 counts and variable B cell function and immunoglobulin levels. Neutropenia has also been reported. Hallmark diagnostic markers of PNP deficiency include hypouricemia, complete or near complete absence of PNP activity in red blood cell lysate and increased urine or blood levels of inosine, guanosine and their deoxy forms. Diagnosis is confirmed by genetic screening of PNP.
 
Differential diagnosis
 
Differential diagnosis includes aplastic anemias, SCID, severe combined immunodeficiency due to adenosine deaminase deficiency, ataxia-telangiectasia, and viral meningoencephalitis.
 
Antenatal diagnosis
 
Measurement of T cell receptor excision circles during newborn screening for SCID can detect some patients suffering from PNP deficiency, although removal of metabolites by maternal PNP may delay the deleterious effects on PNP-deficient lymphocytes. Few newborn screening programs also measure purine metabolites in dried
 
==Treatment==
==Treatment==
 
Management of PNP deficiency involves supportive care and measures to prevent infections. [[Hematopoietic stem cell transplantation]] (HSCT) is currently the only curative treatment, as it can restore normal immune function. Prior to transplantation, patients may receive [[immunoglobulin replacement therapy]] and [[antibiotic prophylaxis]] to reduce the risk of infections.
Supportive treatment, including intravenous immunoglobulin therapy, prophylaxis for Pneumocystis carinii, and physical, occupational, and speech therapy, reduces the risk of infection and may encourage optimal neurologic development for patients.
==Prognosis==
 
The prognosis for individuals with PNP deficiency varies depending on the severity of the condition and the success of treatment. Early diagnosis and intervention, particularly with HSCT, can significantly improve outcomes. Without treatment, the condition can be life-threatening due to severe infections and complications.
==Epidemiology==
PNP-deficiency is extremely rare. Only 33 patients with the disorder in the [[United States]] have been documented.<ref name="pnpone"/> In the United Kingdom only two children have been diagnosed with this disorder in 1994 and 2008.<ref>http://www.channel4.com/news/articles/society/health/boy+first+in+uk+with+rare+condition/3022087</ref>
 
==See also==
==See also==
*[[Nezelof syndrome]]
* [[Primary immunodeficiency]]
 
* [[Hematopoietic stem cell transplantation]]
==References==
* [[Autoimmune disease]]
{{Reflist}}
* [[Lymphocyte]]
== External links ==
[[Category:Genetic disorders]]
{{Medical resources
[[Category:Immunodeficiency]]
|  DiseasesDB    = 11044
|  ICD10          = {{ICD10|D|81|5|d|80}}
|  ICD9          = {{ICD9|277.2}}
|  ICDO          =
|  OMIM          = 613179
|  MedlinePlus    =
|  eMedicineSubj  = ped
|  eMedicineTopic = 1957
|  MeshID        =
|  Orphanet      = 760
}}
{{Immune disorders}}
{{Purine, pyrimidine, porphyrin, bilirubin metabolic pathology}}
 
[[Category:Noninfectious immunodeficiency-related cutaneous conditions]]
[[Category:Autosomal recessive disorders]]
[[Category:Rare diseases]]
[[Category:Rare diseases]]
[[Category:Inborn errors of purine-pyrimidine metabolism]]
[[Category:Combined T and B–cell immunodeficiencies]]
{{dictionary-stub1}}
<gallery>
File:Autosomal_recessive_-_en.svg|Diagram illustrating autosomal recessive inheritance pattern.
</gallery>

Latest revision as of 05:57, 8 April 2025

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
Founder, WikiMD Wellnesspedia &
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Purine nucleoside phosphorylase deficiency
Synonyms PNP deficiency
Pronounce N/A
Specialty N/A
Symptoms Immunodeficiency, neurological disorders, autoimmune disorders
Complications Infections, neurological impairment
Onset Infancy or early childhood
Duration Chronic
Types N/A
Causes Mutations in the PNP gene
Risks Consanguinity
Diagnosis Genetic testing, enzyme assay
Differential diagnosis Severe combined immunodeficiency, Adenosine deaminase deficiency
Prevention Genetic counseling
Treatment Hematopoietic stem cell transplantation, enzyme replacement therapy
Medication N/A
Prognosis Variable, depends on treatment
Frequency Rare
Deaths N/A


A rare genetic disorder affecting the immune system


Purine nucleoside phosphorylase deficiency (PNP deficiency) is a rare genetic disorder that affects the immune system. It is classified as a type of primary immunodeficiency and is caused by mutations in the PNP gene. This condition leads to the accumulation of toxic metabolites, which primarily affect T cells, a type of white blood cell crucial for the immune response.

Pathophysiology[edit]

Purine nucleoside phosphorylase is an enzyme involved in the purine salvage pathway, which is essential for the breakdown and recycling of purines, the building blocks of DNA and RNA. In individuals with PNP deficiency, the enzyme is either absent or non-functional, leading to the accumulation of deoxyguanosine and other toxic metabolites. These substances are particularly harmful to lymphocytes, especially T lymphocytes, resulting in lymphopenia and impaired immune function.

Clinical Features[edit]

Patients with PNP deficiency typically present with recurrent infections due to the compromised immune system. Common infections include those caused by bacteria, viruses, and fungi. In addition to immunodeficiency, affected individuals may exhibit neurological symptoms such as developmental delay, ataxia, and spasticity. Autoimmune disorders, such as autoimmune hemolytic anemia and autoimmune thrombocytopenia, may also occur.

Diagnosis[edit]

The diagnosis of PNP deficiency is based on clinical evaluation, laboratory tests, and genetic analysis. Laboratory findings often reveal low levels of T cells and elevated levels of toxic metabolites in the blood. Genetic testing can confirm mutations in the PNP gene, providing a definitive diagnosis.

Treatment[edit]

Management of PNP deficiency involves supportive care and measures to prevent infections. Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment, as it can restore normal immune function. Prior to transplantation, patients may receive immunoglobulin replacement therapy and antibiotic prophylaxis to reduce the risk of infections.

Prognosis[edit]

The prognosis for individuals with PNP deficiency varies depending on the severity of the condition and the success of treatment. Early diagnosis and intervention, particularly with HSCT, can significantly improve outcomes. Without treatment, the condition can be life-threatening due to severe infections and complications.

See also[edit]

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