Purine Nucleoside Phosphorylase Deficiency malady

NIH Rare Diseases: Purine nucleoside phosphorylase (PNP) deficiency is a primary immunodeficiency syndrome characterized by recurrent infections, neurologic symptoms, and autoimmune disorders. PNP deficiency causes a shortage of white blood cells called T cells that help fight infection. Some people with this condition develop neurologic symptoms, such as spasticity, ataxia, developmental delay, or intellectual disability. In addition, PNP deficiency is associated with increased risk of autoimmune disorders, such as autoimmune hemolytic anemia, idiopathic thrombocytopenia (ITP), autoimmune neutropenia, thyroiditis, and lupus. PNP deficiency is a autosomal recessive disorder caused by mutations in the PNP gene. Treatment with bone marrow transplantation can improve the immune system problems associated with this condition, but does not improve the neurologic symptoms.³⁰

MalaCards: Purine Nucleoside Phosphorylase Deficiency, also known as pnp deficiency, is related to hypouricemia and nucleoside phosphorylase deficiency. An important gene associated with Purine Nucleoside Phosphorylase Deficiency is PNP (purine nucleoside phosphorylase), and among its related pathways are Pentose phosphate pathway and Purine metabolism. The compounds 2,2-difluorodeoxyguanosine and 9-deazaguanine have been mentioned in the context of this disorder. Affiliated tissues include bone marrow, thyroid and skin, and related mouse phenotype renal/urinary system.

Disease Ontology: A combined t cell and b cell immunodeficiency that is a rare autosomal recessive metabolic disorder caused by a mutaion in the pnp gene and characterized mainly by decreased t-cell function.⁶

Genetics Home Reference: 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.¹⁷

Wikipedia: Purine nucleoside phosphorylase deficiency, often called PNP-deficiency, is a rare autosomal...⁴⁴ more...

Aliases & Descriptions:

purine nucleoside phosphorylase deficiency 6 30 17 8 pnp deficiency 6 30 16 17 purine-nucleoside phosphorylase deficiency 6 16 43

nucleoside phosphorylase deficiency 17 deficiency of inosine phosphorylase 6 malnutrition 43

Diseases related to purine nucleoside phosphorylase deficiency by text searches and GeneDecks gene sharing:

(show top 50)    (show all 355)

id	Related Disease	Score	Top Affiliating Genes
1	hypouricemia	32.8	HPRT1, PNP
2	nucleoside phosphorylase deficiency	32.5	LOC647275, FAS, APRT, HPRT1, PNP, AHCY
3	lymphopenia	30.5	FAS, ADA, PNP
4	common variable immunodeficiency	30.4	PNP, FAS, ADA
5	immunodeficiency	29.7	DCK, ADA, ADK, DGUOK, AHCY, PNP
6	adenosine deaminase deficiency	29.0	ADA, DCK, AHCY, PNP, ADK
7	hypermethioninemia	25.1	ADK, AHCY
8	anemia	24.8	FAS, APRT, HPRT1, ADK, AHCY, ADA
9	lesch-nyhan syndrome	24.4	APRT, HPRT1, PNP, PRPS1, PRPS2
10	acute leukemia	23.9	HPRT1, PNP, DCK, FAS
11	leukemia	20.6	DCK, APRT, HPRT1, AHCY, FAS, PNP
12	nezelof syndrome	13.2	PNP, DGUOK
13	mitochondrial dna depletion myopathy	13.1	DGUOK, DCK
14	phosphoribosylpyrophosphate synthetase superactivity	13.0	PRPS1, HPRT1
15	adenine phosphoribosyltransferase deficiency	13.0	APRT, HPRT1
16	urolithiasis	12.6	APRT, HPRT1, PRPS1
17	autoimmune thyroiditis	12.6	FAS, DCK, PNP
18	bcg infection	12.6	FAS, ADA
19	cutaneous t cell lymphoma	12.5	ADA, PNP, FAS
20	cutaneous leishmaniasis	12.4	ADA, PNP, FAS
21	macroglobulinemia	12.4	ADA, DGUOK, DCK
22	hairy cell leukemia	12.4	DCK, ADA
23	combined immunodeficiency	12.4	AHCY, ADA, PNP
24	bilirubin metabolic disorder	12.4	PNP, APRT, ADA
25	severe combined immunodeficiency	12.4	PNP, ADA, AHCY
26	purine-pyrimidine metabolic disorder	12.4	APRT, HPRT1, ADA
27	adult t-cell leukemia	12.3	ADA, FAS, PNP
28	gout	12.3	PRPS1, APRT, PNP, HPRT1
29	hematologic cancer	12.3	PNP, DGUOK, DCK, ADA
30	t-cell leukemia	12.1	PNP, ADA, FAS
31	acute lymphoblastic leukemia	12.0	ADA, DCK, PNP, HPRT1
32	mayer-rokitansky-kuster-hauser syndrome	12.0	APRT, ADA, HPRT1, PNP
33	non-hodgkin lymphoma	11.9	ADA, HPRT1, FAS, PNP
34	xeroderma pigmentosum	11.8	HPRT1, FAS, APRT, ADA
35	hyperuricemia	11.7	APRT, PRPS1, ADA, PRPS2, HPRT1
36	acute myeloid leukemia	11.5	ADA, FAS, PNP, DCK, AHCY
37	pneumonia	11.3	PNP, ADA, PRPS2, HPRT1, APRT, PRPS1
38	down syndrome	11.2	HPRT1, AHCY, DCK, ADA
39	lymphoblastic leukemia	11.2	FAS, HPRT1, PNP, DGUOK, DCK, ADA
40	chronic lymphocytic leukemia	10.9	PNP, ADA, ADK, DCK, DGUOK, FAS
41	colon carcinoma	10.7	PNP, FAS, HPRT1, ADA, ADK, DCK
42	glioblastoma	10.5	APRT, FAS, DCK, ADK, ADA
43	lymphocytic leukemia	10.4	FAS, HPRT1, PNP, DGUOK, DCK, ADK
44	neuroblastoma	10.3	HPRT1, FAS, PNP, ADA, ADK, DCK
45	colorectal cancer	10.1	ADK, PRPS1, AHCY, HPRT1, FAS, ADA
46	tuberculosis	9.7	ADK, APRT, FAS, HPRT1, AHCY, PRPS1
47	protein-energy malnutrition	8.9
48	immunodeficiency due to purine nucleoside phosphorylase deficiency	8.8
49	paraplegia	8.8
50	spastic paraplegia	8.8

Approved drugs:

Drug clinical trials:

Genetic tests related to purine nucleoside phosphorylase deficiency:

id	Genetic test	Affiliating Genes
1	Purine Nucleoside Phosphorylase Deficiency clinical/research	PNP

MalaCards organs/tissues related to purine nucleoside phosphorylase deficiency:

²²

MGI Mouse Phenotypes related to purine nucleoside phosphorylase deficiency:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	renal/urinary system phenotype	MP:0005367	8.1	APRT, FAS, HPRT1, PNP, ADA

Articles related to purine nucleoside phosphorylase deficiency:

(show all 27)

id	Title	Authors	Year	Affiliating Genes
1	Purine nucleoside phosphorylase deficiency with fatal course in two sisters. (19657670)	Aytekin C.... Ikinciogullari A.	2010	PNP
2	Purine nucleoside phosphorylase deficiency in two unr elated Saudi patients. (19584574)	Alangari A.... Hershfield M.	2009	PNP
3	Lentivirus gene therapy for purine nucleoside phosphorylase deficiency. (18924118)	Liao P.... Grunebaum E.	2008	PNP
4	An unconditioned bone marrow transplantation in a child with purine nucleoside phosphorylase deficiency and its unique complication. (18208442)	Aytekin C.... Ikinciogullari A.	2008	PNP
5	Progressive multifocal leukoencephalopathy in purine nucleoside phosphorylase deficiency. (16949240)	Parvaneh N.... Parvaneh L.	2007	PNP
6	Successful HLA-identical hematopoietic stem cell transplantation in a patient with purine nucleoside phosphorylase deficiency. (17910661)	Delicou S.... Grafakos S.	2007	PNP
7	Purine nucleoside phosphorylase deficiency in a patient with spastic paraplegia and recurrent infections. (17641261)	Ozkinay F.... Ozkinay C.	2007	PNP, LOC647275
8	Novel mutations and hot-spots in patients with purine nucleoside phosphorylase deficiency. (15571269)	Grunebaum E.... Roifman C.M.	2004	PNP
9	Purine nucleoside phosphorylase deficiency (PNP-def) presenting with lymphopenia and developmental delay: successful correction with umbilical cord blood transplantation. (15520787)	Myers L.A.... Kurtzberg J.	2004	PNP
10	Purine nucleoside phosphorylase deficiency associated with a dysplastic marrow morphology. (14711904)	Dror Y.... Roifman C.M.	2004	FAS, PNP
11	Familial spastic paraplegia as the presenting manifestation in patients with purine nucleoside phosphorylase deficiency. (12693783)	Tabarki B.... Essoussi A.S.	2003	PNP
12	Purine nucleoside phosphorylase deficiency: a new case report and identification of two novel mutations (Gly156A1a and Val217Ile), only one of which (Gly156A1a) is deleterious. (12483996)	Moallem H.J.... Fikrig S.	2002	PNP
13	Persistent developmental delay despite successful bone marrow transplantation for purine nucleoside phosphorylase deficiency. (11902746)	Baguette C.... Cornu G.	2002	PNP
14	High IL-18 (interferon-gamma inducing factor) concentration in a purine nucleoside phosphorylase deficient patient. (10490534)	Yamamoto T.... Higashino K.	1999	PNP
15	Adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency in common variable immunodeficiency. (9605997)	Fleischman A.... Winkelstein J.A.	1998	ADA, PNP
16	Mutations in purine nucleoside phosphorylase deficiency. (9067751)	Markert M.L.... Ward F.E.	1997	PNP
17	Late diagnosis and correction of purine nucleoside phosphorylase deficiency with allogeneic bone marrow transplantation. (8673045)	Carpenter P.A.... Vowels M.R.	1996	PNP
18	Marked hypouricemia in purine nucleoside phosphorylase deficiency--serendipitous finding on screen. (8665699)	Timms P.M.... Bold A.M.	1996	PNP
19	Liquid-chromatographic study of purine metabolism abnormalities in purine nucleoside phosphorylase deficiency. (8595732)	Chantin C.... Bory C.	1996	PNP
20	Stroke in purine nucleoside phosphorylase deficiency. (7779212)	Tam D.A.... Leshner R.T.	1995	PNP
21	Secondary loss of deoxyguanosine kinase activity in purine nucleoside phosphorylase deficient mice. (7918681)	Snyder F.F.... Mably E.R.	1994	ADK, DCK, PNP
22	Correction of purine nucleoside phosphorylase deficiency by retroviral-mediated gene transfer in mouse S49 T cell lymphoma: a model for gene therapy of T cell immunodeficiency. (1482702)	Foresman M.D.... McIvor R.S.	1992	PNP
23	Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency. (1384322)	Aust M.R.... Markert M.L.	1992	PNP
24	Hypouricemia and cellular immunodeficiency associated with purine-nucleoside phosphorylase deficiency (1929018)	GarcA-a AmorA-n Z.... LA^pez Sastre J.	1991	PNP
25	Purine nucleoside phosphorylase deficiency. (1931007)	Markert M.L.	1991	PNP
26	Mechanisms of deoxyguanosine lymphotoxicity. Human thymocytes, but not peripheral blood lymphocytes accumulate deoxy-GTP in conditions simulating purine nucleoside phosphorylase deficiency. (2104895)	Fairbanks L.D.... Simmonds H.A.	1990	HPRT1, DCK, PNP
27	A human purine nucleoside phosphorylase deficiency caused by a single base change. (3029074)	Williams S.R.... Martin D.W. Jr.	1987	PNP

Genes related to purine nucleoside phosphorylase deficiency according to GeneCards:

(show all 12)

id	Symbol	Description	Score	GeneCards Section Context
1	PNP	purine nucleoside phosphorylase	11.1	Publications
2	LOC647275	purine nucleoside phosphorylase pseudogene	11.1	Publications
3	PRPS2	phosphoribosyl pyrophosphate synthetase 2	11.1
4	PRPS1	phosphoribosyl pyrophosphate synthetase 1	11.1
5	DGUOK	deoxyguanosine kinase	11.1	Publications
6	DCK	deoxycytidine kinase	11.1	Publications
7	APRT	adenine phosphoribosyltransferase	11.1
8	AHCY	adenosylhomocysteinase	11.1
9	HPRT1	hypoxanthine phosphoribosyltransferase 1	11.1	Publications
10	FAS	Fas (TNF receptor superfamily, member 6)	11.1	Publications
11	ADK	adenosine kinase	11.1	Publications
12	ADA	adenosine deaminase	11.1	Publications

Pathways related to purine nucleoside phosphorylase deficiency according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Pentose phosphate pathway20	9.9	PRPS1, PRPS2
2	Purine metabolism38	8.0	ADA, ADK, DGUOK, HPRT1, APRT
3	Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics34	7.8	ADA, ADK, PRPS1, AHCY, HPRT1
4	ATP/ITP metabolism41	7.8	ADA, ADK, PNP, HPRT1, APRT
5	ATP/ITP metabolism10	7.6	ADA, ADK, PNP, HPRT1, APRT
6	Purine metabolism20	6.7	APRT, ADA, ADK, PRPS2, PRPS1, DCK
7	Metabolic pathways20	6.2	ADA, ADK, PRPS2, PRPS1, DCK, DGUOK

Compounds related to purine nucleoside phosphorylase deficiency according to GeneDecks:

(show top 50)    (show all 102)

id	Compound	Score	Top Affiliating Genes
1	2,2-difluorodeoxyguanosine32	9.9	DCK, DGUOK
2	9-deazaguanine32 9 9	11.9	PNP, HPRT1
3	deoxyuridine32 18	10.7	PNP, DGUOK, DCK
4	8-azaguanine32 9 9	11.7	PNP, HPRT1
5	6 thioguanine32	9.6	HPRT1, PNP, DCK
6	2,8-dihydroxyadenine32	9.4	APRT, HPRT1
7	9-(beta-d-arabinofuranosyl)guanine32	9.4	ADA, DCK, DGUOK, PNP
8	nelarabine32 9 9	11.4	PNP, ADA, DCK, DGUOK
9	dgtp32 18	10.3	PNP, DGUOK, DCK, HPRT1
10	adenylosuccinate32	9.3	APRT, ADK, PNP
11	tubercidin32	9.3	AHCY, ADK
12	uric acid32 18	10.2	APRT, PRPS1, HPRT1, PNP
13	Alpha-Phosphoribosylpyrophosphoric Acid9 9	10.2	APRT, HPRT1
14	5-amino-5-deoxyadenosine32	9.2	ADA, ADK
15	allopurinol32 9 9	11.2	HPRT1, ADA, APRT
16	didanosine32 9 9	11.2	ADA, HPRT1, DGUOK, PNP
17	ribose32	9.2	ADK, AHCY, PNP
18	pentostatin32 42 9 9	11.9	ADA, ADK, PNP, DCK
19	cytarabine32 34 9 9	11.9	DGUOK, ADA, DCK, FAS
20	deoxynucleoside32	8.8	DCK, DGUOK, ADK, ADA
21	vidarabine32 9 9	10.8	ADK, DCK, ADA, DGUOK
22	2-chlorodeoxyadenosine32	8.8	DGUOK, PNP, FAS, DCK, ADA
23	ribavirin32 34 9 9	11.7	PNP, AHCY, ADK, ADA
24	fludarabine32 9 9	10.7	ADA, DCK, DGUOK, PNP, FAS
25	guanine32 9 18 9	11.7	ADA, PNP, DCK, APRT, HPRT1
26	2 chloroadenosine32	8.7	AHCY, ADK, DCK, ADA
27	thymidylate32	8.7	HPRT1, DCK, DGUOK, PNP, FAS
28	carbon32	8.5	ADA, PNP, HPRT1, FAS
29	pyrimidine32 18	9.5	ADA, PNP, DCK, DGUOK, ADK
30	guanosine32 9 18 9	11.5	DCK, PNP, ADA, ADK, DGUOK
31	Adenosine9 18 9	10.5	ADA, PNP, AHCY, DCK, ADK
32	5-methylthioadenosine32	8.4	PNP, ADA, ADK, AHCY, APRT
33	inosine monophosphate32	8.4	ADK, AHCY, APRT, HPRT1, PNP
34	s-adenosylhomocysteine32 18	9.4	APRT, PNP, AHCY, ADK, ADA
35	xanthine32 18	9.3	APRT, PNP, ADK, ADA, HPRT1
36	thymidine32 18	9.2	DGUOK, FAS, DCK, APRT, PNP, HPRT1
37	Adenosine monophosphate9 18 9	10.1	ADK, PRPS2, PRPS1, DCK, HPRT1, APRT
38	deoxyguanosine32 18	9.1	DCK, DGUOK, PNP, HPRT1, ADK, ADA
39	deoxycytidine32 18	9.1	ADK, DGUOK, DCK, ADA, PNP, HPRT1
40	inosine32 18	8.9	ADA, ADK, AHCY, PNP, APRT, HPRT1
41	prpp32	7.9	APRT, HPRT1, PNP, ADK, PRPS1, DCK
42	hypoxanthine32 9 18 9	10.9	AHCY, PNP, HPRT1, APRT, ADK, ADA
43	adenine32 9 18 9	10.9	ADK, HPRT1, APRT, PNP, ADA, AHCY
44	pyrophosphate32 18	8.9	PNP, DCK, PRPS2, ADK, APRT, PRPS1
45	deoxyadenosine32 18	8.7	ADA, APRT, PNP, AHCY, DGUOK, DCK
46	adenylate32	7.6	HPRT1, PNP, DGUOK, DCK, ADK, ADA
47	atp32	7.6	APRT, DCK, ADA, ADK, DGUOK, AHCY
48	purine nucleoside32	7.2	APRT, HPRT1, PNP, AHCY, DGUOK, DCK
49	nucleoside32	7.2	HPRT1, ADA, DGUOK, APRT, PNP, AHCY
50	purine32 18	7.9	ADA, APRT, HPRT1, PNP, AHCY, DCK

Cellular components related to purine nucleoside phosphorylase deficiency according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	cytosol	GO:005829	5.8	APRT, ADK, PRPS1, DCK, DGUOK, AHCY

Biological processes related to purine nucleoside phosphorylase deficiency according to GeneDecks:

(show all 13)

id	Name	GO ID	Score	Top Affiliating Genes
1	urate biosynthetic process	GO:034418	10.1	PNP, PRPS1
2	5-phosphoribose 1-diphosphate biosynthetic process	GO:006015	10.0	PRPS2, PRPS1
3	AMP biosynthetic process	GO:006167	9.9	PRPS1, PRPS2
4	nucleoside metabolic process	GO:009116	9.9	PRPS2, PRPS1
5	grooming behavior	GO:007625	9.5	APRT, HPRT1
6	purine nucleotide biosynthetic process	GO:006164	9.5	PRPS1, HPRT1
7	AMP salvage	GO:044209	9.4	APRT, ADK
8	positive regulation of alpha-beta T cell differentiation	GO:046638	9.4	PNP, ADA
9	purine ribonucleoside salvage	GO:006166	8.9	ADK, HPRT1, APRT
10	purine-containing compound salvage	GO:043101	7.5	ADA, ADK, DCK, DGUOK, PNP, HPRT1
11	nucleobase-containing small molecule metabolic process	GO:055086	7.5	ADA, ADK, DCK, DGUOK, PNP, HPRT1
12	purine nucleobase metabolic process	GO:006144	7.2	APRT, ADA, HPRT1, PNP, DGUOK, DCK
13	small molecule metabolic process	GO:044281	6.7	ADA, ADK, PRPS1, DCK, DGUOK, AHCY

Molecular functions related to purine nucleoside phosphorylase deficiency according to GeneDecks:

(show all 7)

id	Name	GO ID	Score	Top Affiliating Genes
1	ribose phosphate diphosphokinase activity	GO:004749	9.9	PRPS2, PRPS1
2	ADP binding	GO:043531	9.8	PRPS1, PRPS2
3	AMP binding	GO:016208	9.6	APRT, PRPS1, PRPS2
4	GDP binding	GO:019003	9.6	PRPS1, PRPS2
5	phosphotransferase activity, alcohol group as acceptor	GO:016773	9.0	ADK, DCK, DGUOK
6	magnesium ion binding	GO:000287	9.0	HPRT1, DCK, PRPS1, PRPS2
7	protein homodimerization activity	GO:042803	9.0	HPRT1, DCK, PRPS1, PRPS2