Purine nucleoside phosphorylase deficiency: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
{{Infobox_Disease | | {{Infobox_Disease | | ||
Name = | Name = Purine nucleoside phosphorylase deficiency | | ||
Image = | | Image = | | ||
Caption = | | Caption = | | ||
| Line 13: | Line 13: | ||
MeshID = | | MeshID = | | ||
}} | }} | ||
{{SI}} | {{SI}} | ||
{{EH}} | {{EH}} | ||
__NOTOC__ | __NOTOC__ | ||
==Overview== | ==Overview== | ||
'''Purine nucleoside phosphorylase deficiency''' is a rare congenital [[immunodeficiency]] of [[purine nucleoside phosphorylase]]. | '''Purine nucleoside phosphorylase deficiency''', often called '''PNP-deficiency''', is a rare congenital [[immunodeficiency]] of [[purine nucleoside phosphorylase]]. This enzyme is important in the purine degradation pathway. A deficiency of it causes [[T-cell]] immunodeficiency. It is also often associated with neurological disorders such as [[mental retardation]]. This[[autosomal recessive]] [[metabolic disorder]] which results in [[severe combined immunodeficiency]]. | ||
==Pathophysiology== | |||
The disorder is caused by a disruption of the [[purine nucleoside phosphorylase]], a key enzyme in the purine salvage pathway. | |||
This enzyme is required for [[purine]] degradation. Specifically, it catalyzes the conversion of inosine and guanosine to [[hypoxanthine]]. A deficiency of it leads to build up of elevated deoxy-GTP (dGTP) levels resulting in [[T-cell]] toxicity and deficiency.<ref name="pmid9122228">{{cite journal |author=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=2522–7 |year=1997 |month=March |pmid=9122228 |pmc=20121 |doi= 10.1073/pnas.94.6.2522|url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=9122228}}</ref><ref name="pmid16964310">{{cite journal |author=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=2717–26 |year=2006 |month=October |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 |format= |work= |accessdate=}}</ref> | |||
==Symptoms== | |||
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 disorder]]s. [[lupus erythematosus|Lupus]]-erythematosis, 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> | |||
Neurological symptoms, such as developmental decline, [[hypotonia]], and [[mental retardation]] have also been reported. | |||
==Genetic prevalence== | |||
[[Image:autorecessive.svg|thumb|right|Purine nucleoside phosphorylase deficiency has an autosomal recessive pattern of inheritance.]] | |||
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 one child has been diagnosed with this disorder. <ref>http://www.channel4.com/news/articles/society/health/boy+first+in+uk+with+rare+condition/3022087</ref> | |||
==References== | |||
{{reflist}} | |||
{{SIB}} | |||
{{Immune disorders}} | {{Immune disorders}} | ||
{{ | {{Purine, pyrimidine, porphyrin, bilirubin metabolic pathology}} | ||
[[Category:Noninfectious immunodeficiency-related cutaneous conditions]] | |||
[[Category:Genetic disorders]] | |||
[[Category:Autosomal recessive disorders]] | |||
[[Category:Rare diseases]] | |||
[[Category:Rheumatology]] | [[Category:Rheumatology]] | ||
[[Category:Congenital Disease]] | [[Category:Congenital Disease]] | ||
Revision as of 18:11, 26 January 2010
| Purine nucleoside phosphorylase deficiency | |
| ICD-10 | D81.5 |
|---|---|
| ICD-9 | 277.2 |
| OMIM | 164050 |
| DiseasesDB | 11044 |
| eMedicine | ped/1957 |
Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
Overview
Purine nucleoside phosphorylase deficiency, often called PNP-deficiency, is a rare congenital immunodeficiency of purine nucleoside phosphorylase. This enzyme is important in the purine degradation pathway. A deficiency of it causes T-cell immunodeficiency. It is also often associated with neurological disorders such as mental retardation. Thisautosomal recessive metabolic disorder which results in severe combined immunodeficiency.
Pathophysiology
The disorder is caused by a disruption of the purine nucleoside phosphorylase, a key enzyme in the purine salvage pathway.
This enzyme is required for purine degradation. Specifically, it catalyzes the conversion of inosine and guanosine to hypoxanthine. A deficiency of it leads to build up of elevated deoxy-GTP (dGTP) levels resulting in T-cell toxicity and deficiency.[1][2]
In contrast to adenosine deaminase deficiency (another deficiency of purine metabolism), there is minimal disruption to B cells.[3]
Symptoms
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-erythematosis, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura have been reported with PNP-deficiency.[4]
Neurological symptoms, such as developmental decline, hypotonia, and mental retardation have also been reported.
Genetic prevalence
PNP-deficiency is extremely rare. Only 33 patients with the disorder in the United States have been documented.[4] In the United Kingdom only one child has been diagnosed with this disorder. [5]
References
- ↑ Snyder FF, Jenuth JP, Mably ER, Mangat RK (1997). "Point mutations at the purine nucleoside phosphorylase locus impair thymocyte differentiation in the mouse". Proc. Natl. Acad. Sci. U.S.A. 94 (6): 2522–7. doi:10.1073/pnas.94.6.2522. PMC 20121. PMID 9122228. Unknown parameter
|month=ignored (help) - ↑ Toro A, Grunebaum E (2006). "TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice". J. Clin. Invest. 116 (10): 2717–26. doi:10.1172/JCI25052. PMC 1560347. PMID 16964310. Unknown parameter
|month=ignored (help) - ↑ "eMedicine - Purine Nucleoside Phosphorylase Deficiency : Article by Alan P Knutsen".
- ↑ 4.0 4.1 Markert ML (1991). "Purine nucleoside phosphorylase deficiency". Immunodefic Rev. 3 (1): 45–81. PMID 1931007.
- ↑ http://www.channel4.com/news/articles/society/health/boy+first+in+uk+with+rare+condition/3022087
Template:Purine, pyrimidine, porphyrin, bilirubin metabolic pathology