Adenosine Deaminase Deficiency malady

Genetics Home Reference: Adenosine deaminase (ADA) deficiency is an inherited disorder that damages the immune system and causes severe combined immunodeficiency (SCID). Children with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They 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 experience pneumonia, chronic diarrhea, and widespread skin rashes, and grow much more slowly than healthy children. Some also have neurological problems such as developmental delay, movement disorders, and hearing loss. If not treated in a way that restores immune function, children with SCID usually live only a year or two.¹⁷

MalaCards: Adenosine Deaminase Deficiency, also known as ada deficiency, is related to combined immunodeficiency and severe combined immunodeficiency. An important gene associated with Adenosine Deaminase Deficiency is ADA (adenosine deaminase), and among its related pathways are Purine metabolism and Pyrimidine metabolism. The drug pegademase bovine and the compounds deoxyinosine and neplanocin a have been mentioned in the context of this disorder. Affiliated tissues include bone marrow, small intestine and liver, and related mouse phenotypes are respiratory system and immune system.

Disease Ontology: A severe combined immunodeficiency that is caused by a defective enzyme, adenosine deaminase (ada), necessary for the breakdown of purines. lack of ada causes accumulation of datp.⁶

Wikipedia: Adenosine deaminase deficiency, also called ADA deficiency or ADA-SCID, is an autosomal...⁴⁴ more...

GeneReviews summary for ada

Aliases & Descriptions:

adenosine deaminase deficiency 6 7 15 30 17 8 32 43 ada deficiency 15 30 16 17 severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-negative, due to adenosine deaminase deficiency 30 17 43 adenosine-deaminase deficiency 6 16 scid due to ada deficiency 30 17 ada-scid 30 17 severe combined immunodeficiency due to adenosine deaminase deficiency 30

adenosine deaminase deficient severe combined immunodeficiency 30 severe combined immunodeficiency due to ada deficiency 30 deficiency of adenosine deaminase (disorder) 6 adenosine deaminase deficiency (disorder) 6 severe combined immunodeficiency 43 malnutrition 43 ada 6

Diseases related to adenosine deaminase deficiency by text searches and GeneDecks gene sharing:

(show top 50)    (show all 536)

id	Related Disease	Score	Top Affiliating Genes
1	combined immunodeficiency	34.7	BCL2, ADA, AHCY, PNP
2	severe combined immunodeficiency	34.5	BCL2, PNP, ADA, AHCY
3	immunodeficiency	31.6	DCK, ADK, ADA, ITPA, GBA, DNTT
4	chronic granulomatous disease	29.5	OTC, ADA
5	gaucher's disease	28.4	ADA, GBA
6	progressive multifocal leukoencephalopathy	28.3	PNP, ADA
7	hairy cell leukemia	28.2	DCK, ADA
8	burkitt's lymphoma	27.9	BCL2, PNP, DNTT, DCK, ADA
9	t-cell leukemia	27.7	BCL2, PNP, ADA
10	nucleoside phosphorylase deficiency	27.7	AHCY, DCK, ADK, ADA, PNP
11	purine nucleoside phosphorylase deficiency	27.7	AHCY, DCK, ADK, ADA, PNP
12	acquired immunodeficiency syndrome	27.6	ADA, DCK, PNP
13	thymoma	27.5	ADA, BCL2, DNTT
14	leukemia/lymphoma	27.4	ADA, BCL2, PNP
15	adult t-cell leukemia	27.3	DNTT, BCL2, ADA
16	chronic myeloid leukemia	27.1	BCL2, PNP, ADA, DNTT
17	thyroiditis	27.1	DCK, ITPA, ADA, DNTT, PNP, BCL2
18	non-hodgkin lymphoma	27.1	ADA, DNTT, PNP, BCL2
19	toxoplasmosis	27.0	ADA, BCL2, ADK
20	dementia	26.9	ADA, DNTT, GBA, BCL2
21	tuberculosis	26.7	PNP, BCL2, ITPA, ADA, ADK, AHCY
22	psoriasis	26.6	BCL2, PNP, DNTT, GBA, ADA
23	acute lymphoblastic leukemia	26.2	ADA, DCK, DNTT, ITPA, BCL2
24	pneumonia	26.2	PNP, OTC, ADA, BCL2, ITPA
25	anemia	26.0	BCL2, ITPA, AHCY, ADA, ADK, GBA
26	rheumatoid arthritis	25.9	ADA, DNTT, PNP, ITPA, BCL2
27	lymphoblastic leukemia	25.9	ADA, DNTT, BCL2, ITPA, PNP, DCK
28	cerebritis	25.8	BCL2, OTC, DNTT, ADK, ADA
29	macroglobulinemia	25.5	DCK, ADA, BCL2
30	fibrosis	25.5	BCL2, GBA, ADA, OTC, ADK
31	myeloid leukemia	25.4	BCL2, GBA, DNTT, ADA, AHCY, DCK
32	hypermethioninemia	25.3	AHCY, ADK
33	myeloma	24.9	BCL2, GBA, OTC, ADA, ADK, DNTT
34	alzheimer's disease	24.8	PNP, BCL2, ADA, OTC, ADK, DNTT
35	acute leukemia	24.3	PNP, BCL2, DCK, DNTT
36	acute myeloid leukemia	23.8	DCK, AHCY, PNP, DNTT, ADA, BCL2
37	neuroblastoma	23.2	AHCY, PNP, BCL2, DCK, ADA, ADK
38	leukemia	23.2	DNTT, BCL2, OTC, AHCY, ITPA, GBA
39	chronic lymphocytic leukemia	23.1	PNP, ADK, ADA, BCL2, DCK, DNTT
40	lymphocytic leukemia	23.1	DNTT, BCL2, PNP, ADK, ADA, DCK
41	colon carcinoma	22.9	OTC, PNP, DCK, ADK, ADA, BCL2
42	carcinoma	22.9	ADK, DCK, ADA, PNP, OTC, BCL2
43	gaucher disease type 1	13.2	ADA, GBA
44	familial hypercholesterolemia	12.9	ADA, OTC
45	thymic epithelial tumor	12.6	BCL2, DNTT
46	glycogen storage disease	12.5	AHCY, OTC, GBA
47	thymic carcinoma	12.4	DNTT, BCL2
48	follicular lymphoma	12.3	DNTT, DCK, BCL2
49	hematologic cancer	12.3	DNTT, PNP, DCK, ADA
50	bilirubin metabolic disorder	12.3	GBA, ADA, PNP, OTC

Approved drugs:

Drug clinical trials:

Inferred drug relations via UMLS/NDF-RT:

^43 28 pegademase bovine

Genetic tests related to adenosine deaminase deficiency:

id	Genetic test	Affiliating Genes
1	Adenosine Deaminase Deficiency clinical/research	ADA

MalaCards organs/tissues related to adenosine deaminase deficiency:

²²

MGI Mouse Phenotypes related to adenosine deaminase deficiency:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	respiratory system phenotype	MP:0005388	8.1	BCL2, ITPA, ADK, ADA, GBA
2	immune system phenotype	MP:0005387	7.1	GBA, ADA, DCK, DNTT, PNP, OTC
3	hematopoietic system phenotype	MP:0005397	7.0	BCL2, GBA, ADA, DCK, DNTT, PNP
4	cellular phenotype	MP:0005384	6.9	GBA, ADA, DCK, DNTT, PNP, OTC

Articles related to adenosine deaminase deficiency:

(show top 50)    (show all 96)

id	Title	Authors	Year	Affiliating Genes
1	Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency. (21725047)	Sokolic R.... Candotti F.	2011	ADA
2	Gene therapy for adenosine deaminase deficiency. (20493400)	Cappelli B.... Aiuti A.	2010	ADA
3	Gene therapy for immunodeficiency due to adenosine deaminase deficiency. (19179314)	Aiuti A.... Roncarolo M.G.	2009	ADA
4	Restoration of adenosine deaminase-deficient human thymocyte development in vitro by inhibition of deoxynucleoside kinases. (19018008)	Joachims M.L.... Thompson L.F.	2008	ADA, ADK, DCK
5	Adenosine deaminase deficiency can present with features of Omenn syndrome. (18243287)	Roifman C.M.... Mandel K.	2008	ADA
6	Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications. (17185467)	HAPnig M.... Friedrich W.	2007	ADA
7	Neurologic abnormalities in patients with adenosine deaminase deficiency. (17765813)	Nofech-Mozes Y.... Roifman C.M.	2007	ADA
8	Autoimmune thyroiditis and acquired hypothyroidism in an infant with severe combined immunodeficiency due to adenosine deaminase deficiency. (17614781)	Nagpala P.... Gottschalk M.	2007	ADA
9	Burkitt's lymphoma in a patient with adenosine deaminase deficiency-severe combined immunodeficiency treated with polyethylene glycol-adenosine deaminase. (17586199)	Husain M.... Roifman C.M.	2007	ADA
10	Gene therapy for adenosine deaminase deficiency (15773344)	Sakiyama Y.... Ohtsu M.	2005	ADA
11	Polyethylene glycol-conjugated adenosine phosphorylas e: development of alternative enzyme therapy for adenosine deaminase deficiency . (12633906)	Brewerton L.J.... Snyder F.F.	2003	ADA
12	Adenosine deaminase deficiency with mosaicism for a 'second-site suppressor' of a splicing mutation: decline in revertant T lymphocytes during enzyme replacement therapy. (11807006)	Arredondo-Vega F.X.... Hershfield M.S.	2002	ADA
13	Cognitive and behavioral abnormalities in adenosine deaminase deficient severe combined immunodeficiency. (11445793)	Rogers M.H.... Gaspar H.B.	2001	ADA
14	Metabolites from apoptotic thymocytes inhibit thymopoiesis in adenosine deaminase-deficient fetal thymic organ cultures. (11067867)	Thompson L.F.... Resta R.	2000	ADA
15	Adenosine deaminase deficiency as the first target disorder in gene therapy. (11060694)	Onodera M.... Sakiyama Y.	2000	ADA
16	Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombination. (10079104)	Gangi-Peterson L.... Mitchell B.S.	1999	ADA, PNP, DNTT
17	Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency. (9414266)	Onodera M.... Sakiyama Y.	1998	ADA
18	Treatment of adenosine deaminase deficiency. (18020547)	Hoogerbrugge P.M.... Valerio D.	1998	ADA
19	Adenosine deaminase-deficient mice generated using a two-stage genetic engineering strategy exhibit a combined immunodeficiency. (9478961)	Blackburn M.R.... Kellems R.E.	1998	ADA, AHCY
20	Adenosine deaminase deficiency: clinical expression, molecular basis, and therapy. (9801258)	Hershfield M.S.	1998	ADA
21	New models for the study of adenosine deaminase deficiency. (9598108)	Thompson L.F.	1998	ADA
22	Adenosine deaminase deficiency (9833480)	Okawa H.	1998	ADA
23	Glaxo/MRS Young Investigator Medal. Molecular studies on adenosine deaminase deficiency and hereditary haemorrhagic telangiectasia. (9616253)	Shovlin C.L.	1998	ADA
24	Cost analysis of treatments for severe combined immunodeficiency patients caused by adenosine deaminase deficiency: comparison of gene therapy and bone marrow transplantation. (9612707)	Imai H.	1998	ADA
25	Generation of normal lymphocyte populations following transplantation of adenosine-deaminase-deficient fetal liver cells. (9193758)	Migchielsen A.A.... Valerio D.	1997	ADA
26	Adenosine deaminase deficiency in adults. (9108404)	Ozsahin H.... Hershfield M.S.	1997	ADA
27	Keratinocyte gene therapy for adenosine deaminase deficiency: a model approach for inherited metabolic disorders. (9195213)	Fenjves E.S.... Taichman L.B.	1997	ADA
28	SCID: the role of adenosine deaminase deficiency. (9267078)	Resta R.... Thompson L.F.	1997	ADA
29	Full genetic rescue of adenosine deaminase-deficient mice through introduction of the human gene. (8894685)	Migchielsen A.A.... Valerio D.	1996	ADA
30	Sensorineural deafness in siblings with adenosine deaminase deficiency. (8879650)	Tanaka C.... Takeshita K.	1996	ADA
31	p53 expression is required for thymocyte apoptosis induced by adenosine deaminase deficiency. (7667298)	Benveniste P.... Cohen A.	1995	ADA
32	Heterogeneity of phenotype in two siblings with adenosine deaminase deficiency. (8120281)	Umetsu D.T.... Hershfield M.S.	1994	ADA
33	Homozygosity for a missense mutation (G20R) associated with neonatal onset adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID). (8299233)	Yang D.R.... Hirschhorn R.	1994	ADA
34	Long-term culture and T cell receptor analysis of T cell clones isolated from a patient with adenosine deaminase deficiency and type I diabetes. (7955566)	De Berardinis P.... Guardiola J.	1994	ADA
35	Correct splicing despite mutation of the invariant first nucleotide of a 5' splice site: a possible basis for disparate clinical phenotypes in siblings with adenosine deaminase deficiency. (8178821)	Arredondo-Vega F.X.... Hershfield M.S.	1994	ADA
36	Genetic manipulation of hematopoietic stem cells in adenosine deaminase deficiency. (7660937)	Williams D.A.... Moritz T.	1994	ADA
37	Somatic mosaicism for a newly identified splice-site mutation in a patient with adenosine deaminase-deficient immunodeficiency and spontaneous clinical recovery. (8023852)	Hirschhorn R.... Ownby D.R.	1994	ADA
38	Gene therapy techniques in the treatment of adenosine deaminase--deficiency severe combined immune deficiency syndrome. (8151512)	Noonan N.A.... Senner A.M.	1994	ADA
39	Development of gene therapy for immunodeficiency: adenosine deaminase deficiency. (8433875)	Blaese R.M.	1993	ADA
40	Treatment of severe combined immunodeficiency disease (SCID) due to adenosine deaminase deficiency with CD34+ selected autologous peripheral blood cells transduced with a human ADA gene. Amendment to clinical research project, Project 90-C-195, January 10, 1992. (7691188)	Blaese R.M.... Berger M.	1993	ADA
41	Bone marrow gene therapy for adenosine deaminase deficiency. (7909479)	Kaptein L.C.... van Beusechem V.W.	1993	ADA
42	IgG antibody response to polyethylene glycol-modified adenosine deaminase in patients with adenosine deaminase deficiency. (1569204)	Chaffee S.... Hershfield M.S.	1992	ADA
43	Antibody responses to bacteriophage phi X174 in patients with adenosine deaminase deficiency. (1387561)	Ochs H.D.... Hershfield M.S.	1992	ADA
44	Effects of deoxyadenosine on ribonucleotide reductase in adenosine deaminase-deficient lymphocytes. (1830628)	Takeda E.... Miyao M.	1991	ADA
45	Donor type natural killer cells after haploidentical T cell-depleted bone marrow stem cell transplantation in a patient with adenosine deaminase-deficient severe combined immunodeficiency. (1712689)	Gaines A.D.... Buckley R.H.	1991	ADA
46	Adenosine deaminase deficiency. (2078332)	Hirschhorn R.	1990	ADA
47	Immunodeficiency secondary to adenosine deaminase deficiency and purine nucleoside phosphorylation deficiency. (2115692)	Carson D.A.... Carrera C.J.	1990	ADA
48	Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combine immunodeficiency. (1974554)	Arredondo-Vega F.X.... Hershfield M.S.	1990	ADA
49	Inosine triphosphate pyrophosphohydrolase deficiency in a kindred with adenosine deaminase deficiency. (2167185)	Duley J.A.... Levinsky R.J.	1990	ADA, ITPA
50	Structure of adenosine deaminase mRNAs from normal and adenosine deaminase-deficient human cell lines. (6208479)	Adrian G.S.... Hutton J.	1984	ADA

Genes related to adenosine deaminase deficiency according to GeneCards:

id	Symbol	Description	Score	GeneCards Section Context
1	ADA	adenosine deaminase	11.1	Publications
2	PNP	purine nucleoside phosphorylase	11.1	Publications
3	GBA	glucosidase, beta, acid	11.1
4	AHCY	adenosylhomocysteinase	11.0	Publications
5	ITPA	inosine triphosphatase (nucleoside triphosphate pyrophosphatase)	11.0	Publications
6	DNTT	deoxynucleotidyltransferase, terminal	11.0	Publications
7	DCK	deoxycytidine kinase	11.0	Publications
8	OTC	ornithine carbamoyltransferase	11.0	Publications
9	ADK	adenosine kinase	11.0	Publications
10	BCL2	B-cell CLL/lymphoma 2	11.0	Publications

Pathways related to adenosine deaminase deficiency according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Purine metabolism38	9.4	ADK, ADA
2	Pyrimidine metabolism20	8.9	ITPA, PNP, DCK
3	Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics34	8.7	ITPA, AHCY, ADK, ADA
4	ATP/ITP metabolism41	8.6	ADA, ADK, PNP, ITPA
5	ATP/ITP metabolism10	8.5	ADA, ADK, PNP, ITPA
6	Purine metabolism20	8.2	ADA, ADK, DCK, PNP, ITPA
7	Metabolic pathways20	6.9	GBA, ADA, ADK, DCK, AHCY, PNP

Compounds related to adenosine deaminase deficiency according to GeneDecks:

(show top 50)    (show all 87)

id	Compound	Score	Top Affiliating Genes
1	deoxyinosine32 18	11.1	ADA, PNP
2	neplanocin a32	10.0	ADA, AHCY
3	cordycepin32	9.8	ADA, DNTT
4	9-(beta-d-arabinofuranosyl)guanine32	9.7	DCK, ADA, PNP
5	nelarabine32 9 9	11.7	ADA, PNP, DCK
6	5-amino-5-deoxyadenosine32	9.7	ADK, ADA
7	8-phenyltheophylline32	9.6	ADA, ADK
8	8-cyclopentyltheophylline32	9.6	ADA, ADK
9	tubercidin32	9.6	AHCY, ADK
10	6 thioguanine32	9.6	DCK, ITPA, PNP
11	n(6)-cyclohexyladenosine32	9.5	ADK, ADA
12	parathion32 18	10.5	DCK, DNTT, PNP
13	xanthosine 5-triphosphate32 18	10.4	PNP, ITPA
14	triphosphate32 18	10.4	ITPA, DNTT, DCK
15	n6-cyclopentyladenosine32	9.4	ADA, ADK
16	cytidine32 9 18 9	12.4	DNTT, ADA, DCK
17	nitrobenzylthioinosine32	9.4	ADA, ADK
18	ribose32	9.3	ADK, PNP, AHCY
19	erythro-9-(2 hydroxy 3-nonyl)adenine32	9.3	ADA, ADK
20	deoxynucleoside32	9.2	ADA, ADK, DCK
21	vidarabine32 9 9	11.2	DCK, ADK, ADA
22	dgtp32 18	10.2	DCK, DNTT, ITPA, PNP
23	prpp32	9.1	PNP, DCK, ADK
24	5-methylthioadenosine32	9.1	ADA, PNP, ADK, AHCY
25	dipyridamole42 32 9 9	12.1	ADK, ADA, DCK
26	hypoxanthine32 9 18 9	12.0	PNP, AHCY, ADK, ADA
27	s-adenosylhomocysteine32 18	10.0	ADK, PNP, ADA, AHCY
28	xanthine32 18	10.0	ADK, ADA, PNP
29	adenine32 9 18 9	12.0	ADA, PNP, ADK, AHCY
30	inosine monophosphate32	8.9	PNP, ITPA, AHCY, ADK
31	pentostatin32 42 9 9	11.9	ADA, PNP, ADK, DCK
32	deoxyguanosine32 18	9.9	PNP, DCK, ADK, ADA
33	deoxycytidine32 18	9.9	DCK, ADK, ADA, PNP
34	2 chloroadenosine32	8.9	AHCY, ADA, DCK, ADK
35	guanosine32 9 18 9	11.9	PNP, DCK, ADK, ADA
36	methotrexate32 34 42 9 9	12.8	ITPA, ADA, DNTT, DCK, GBA
37	2-chlorodeoxyadenosine32	8.8	BCL2, ADA, PNP, DCK, DNTT
38	fludarabine32 9 9	10.8	PNP, DCK, DNTT, BCL2, ADA
39	5fluorouracil32	8.8	BCL2, PNP, OTC, DCK
40	inosine32 18	9.7	ADA, ADK, ITPA, AHCY, PNP
41	ribavirin32 34 9 9	11.7	ITPA, ADA, ADK, PNP, AHCY
42	Adenosine9 18 9	10.6	PNP, AHCY, DCK, ADA, ADK
43	deoxyadenosine32 18	9.6	PNP, DCK, ADK, ADA, AHCY
44	pyrimidine32 18	9.3	ADK, ADA, DCK, PNP, OTC
45	pyrophosphate32 18	9.3	ADK, DCK, DNTT, PNP, ITPA
46	purine nucleoside32	8.1	DCK, DNTT, AHCY, PNP, ADK, ADA
47	nucleoside32	8.1	AHCY, DNTT, PNP, DCK, ADK, ADA
48	adenylate32	8.1	DNTT, PNP, GBA, DCK, ADK, ADA
49	purine32 18	8.7	PNP, ITPA, ADA, ADK, DCK, DNTT
50	atp32	7.4	PNP, AHCY, DNTT, DCK, ADA, OTC

Cellular components related to adenosine deaminase deficiency according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	cytosol	GO:005829	7.6	BCL2, PNP, AHCY, DCK, ADK, ADA

Biological processes related to adenosine deaminase deficiency according to GeneDecks:

(show all 7)

id	Name	GO ID	Score	Top Affiliating Genes
1	positive regulation of alpha-beta T cell differentiation	GO:046638	9.8	PNP, ADA
2	response to hydrogen peroxide	GO:042542	9.7	BCL2, ADA
3	positive regulation of B cell proliferation	GO:030890	9.4	BCL2, ADA
4	purine-containing compound salvage	GO:043101	8.7	PNP, DCK, ADK, ADA
5	purine nucleobase metabolic process	GO:006144	8.6	ADA, ADK, DCK, PNP
6	nucleobase-containing small molecule metabolic process	GO:055086	8.6	PNP, DCK, ADK, ADA
7	small molecule metabolic process	GO:044281	7.2	GBA, ADA, ADK, DCK, AHCY, PNP

Molecular functions related to adenosine deaminase deficiency according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	phosphate ion binding	GO:042301	9.2	OTC, PNP
2	phosphotransferase activity, alcohol group as acceptor	GO:016773	9.1	DCK, ADK