Canavan Disease malady

NIH Rare Diseases: Canavan disease is an inherited disorder that causes progressive damage to nerve cells in the brain. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by degeneration of myelin, which is the fatty covering that insulates nerve fibers. Canavan disease is caused by mutations in the ASPA gene and is inherited in an autosomal recessive pattern. While it occurs in people of all ethnic backgrounds, it is most common in people of Ashkenazi (eastern and central European) Jewish heritage, and among Saudi Arabians. ³⁰

MalaCards: Canavan Disease, also known as aspartoacylase deficiency, is related to succinic semialdehyde dehydrogenase deficiency and hypotonia. An important gene associated with Canavan Disease is ASPA (aspartoacylase), and among its related pathways is Alanine, aspartate and glutamate metabolism. The compounds n-acetyl-aspartyl-glutamate and n-acetylaspartate have been mentioned in the context of this disorder. Affiliated tissues include brain, skin and fetal brain, and related mouse phenotypes are muscle and nervous system.

NINDS: Canavan disease is a gene-linked neurological disorder in which the brain degenerates into spongy tissue riddled with microscopic fluid-filled spaces. Canavan disease has been classified as one of a group of genetic disorders known as the leukodystrophies but--unlike most leukodystrophies. Recent research has indicated that the cells in the brain responsible for making myelin sheaths, known as oligodendrocytes, cannot properly complete this critical developmental task. ³¹

Genetics Home Reference: Canavan disease is an inherited disorder that causes progressive damage to nerve cells in the brain. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by degeneration of myelin, which is the fatty covering that insulates nerve fibers.¹⁷

Wikipedia: Canavan disease, also called Canavan-Van Bogaert-Bertrand disease, aspartoacylase deficiency or...⁴⁴ more...

OMIM: 271900

GeneReviews summary for canavan

Aliases & Descriptions:

canavan disease 6 7 44 15 30 16 17 31 33 8 32 43 aspartoacylase deficiency 44 15 30 16 17 aspa deficiency 44 15 30 16 17 von bogaert-bertrand disease 44 30 17 aminoacylase 2 deficiency 44 30 17 acy2 deficiency 44 30 17 asp deficiency 44 30 17 spongy degeneration of white matter in infancy 44 17 spongy degeneration of central nervous system 44 17

canavan-van bogaert-bertrand disease 6 30 spongy degeneration of the brain 44 17 van bogaert-bertrand syndrome 44 17 leukodystrophy, spongiform 44 17 spongy degeneration of central nervous system (disorder) 6 spongy degeneration of the central nervous system 30 spongy degeneration 43 leukodystrophies 17 leukodystrophy 43

Diseases related to canavan disease by text searches and GeneDecks gene sharing:

(show top 50)    (show all 73)

id	Related Disease	Score	Top Affiliating Genes
1	succinic semialdehyde dehydrogenase deficiency	27.7	GLUD1, ALDH5A1, GPT, ASPA
2	hypotonia	27.6	GLUD1, ALDH5A1, GPT, ASPA
3	neuronitis	23.0	GABRA6, NEU1, SLC1A6, AKAP5, GLUD1, CACNB3
4	progressive muscular atrophy	13.2	FOLH1, NEU1
5	drug-induced hepatitis	12.5	GLUD1, GPT
6	sialuria	12.5	NEU1, MID1
7	alcohol abuse	12.4	GRIA3, GPT, NEU1
8	alcoholism	12.4	GPT, GLUD1, NEU1
9	small cell carcinoma	12.3	BRCA1, FOLH1, GPT
10	bilirubin metabolic disorder	12.1	NEU1, GLUD1, ALDH5A1
11	mayer-rokitansky-kuster-hauser syndrome	11.9	BRCA1, ASPA, MID1, ALDH5A1
12	epilepsy syndrome	11.7	NEU1, GLUD1, ALDH5A1, GRIA3, ASPA, FOLH1
13	metachromatic leukodystrophy	11.5
14	seizures	11.5	SLC1A6, GLUD1, ALDH5A1, GRIA3, ASPA, FOLH1
15	ischemia	11.2	GRIA3, GPT, ALDH5A1, GLUD1, SLC1A6
16	schizophrenia	10.8	GABRA6, SLC1A6, GLUD1, ALDH5A1, GPT, GRIA3
17	krabbe disease	9.2
18	alexander disease	8.5
19	pelizaeus-merzbacher disease	7.7
20	aminoacylase deficiency	7.3
21	metachromatic leukodystrophy due to saposin b deficiency	7.3
22	tremor	7.2
23	leukodystrophy	7.2
24	leukodystrophy, dysmyelinating, and spastic paraparesis with or without dystonia	7.0
25	leukodystrophy, hypomyelinating 3	7.0
26	leukodystrophy, adult-onset, autosomal dominant	7.0
27	pol iii-related leukodystrophies	7.0
28	pelizaeus-merzbacher-like disease 1	6.8
29	vasculopathy, retinal, with cerebral leukodystrophy	6.8
30	hypomyelination and congenital cataract	6.8
31	leukoencephalopathy with vanishing white matter	6.8
32	megalencephalic leukoencephalopathy with subcortical cysts	6.8
33	bovine spongiform encephalopathy	6.7
34	aicardi-goutieres syndrome	6.4
35	adrenoleukodystrophy	6.4
36	csf1r-related hereditary diffuse leukoencephalopathy with spheroids	6.4
37	hereditary diffuse leukoencephalopathy with spheroids	6.4
38	leukodystrophy reunion type	6.4
39	leukodystrophy with oligodontia	6.4
40	leukodystrophy, pseudometachromatic	6.4
41	leukodystrophy, hypomyelinating, 4	6.4
42	metachromatic leukodystrophy due to deficiency of sap	6.4
43	metachromatic leukodystrophy due to sap-b deficiency	6.4
44	antisocial personality disorder	6.3
45	aminoacylase 1 deficiency	6.0
46	hypomyelination with atrophy of basal ganglia and cerebellum	5.9
47	zellweger syndrome	5.9
48	zellweger syndrome spectrum	5.9
49	ataxia	4.9
50	neuropathy	4.9

Clinical features from OMIM: 271900

Approved drugs:

Drug clinical trials:

Genetic tests related to canavan disease:

id	Genetic test	Affiliating Genes
1	Canavan Disease clinical/research	ASPA

MalaCards organs/tissues related to canavan disease:

²²

MGI Mouse Phenotypes related to canavan disease:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	muscle phenotype	MP:0005369	8.1	CACNB3, ALDH5A1, MID1, ASPA, BRCA1, NEU1
2	nervous system phenotype	MP:0003631	7.4	BRCA1, NEU1, AKAP5, CACNB3, GRIA3, MID1
3	behavior/neurological phenotype	MP:0005386	6.4	GABRA6, NEU1, AKAP5, CACNB3, ALDH5A1, GRIA3

Articles related to canavan disease:

(show top 50)    (show all 69)

id	Title	Authors	Year	Affiliating Genes
1	Impact of gene patents and licensing practices on acc ess to genetic testing and carrier screening for Tay-Sachs and Canavan disease. (20393311)	Colaianni A.... Cook-Deegan R.	2010	ASPA
2	Are astrocytes the missing link between lack of brain aspartoacylase activity and the spongiform leukodystrophy in Canavan disease? (19319678)	Baslow M.H.... Guilfoyle D.N.	2009	GRIA3, ASPA
3	Glyceryl triacetate for Canavan disease: a low-dose t rial in infants and evaluation of a higher dose for toxicity in the tremor rat model. (19685155)	Madhavarao C.N.... Namboodiri A.M.	2009	ASPA
4	Long term clinical course of Canavan disease--a rare Japanese case (19764455)	Mizuguchi K.... Kubota M.	2009	ASPA
5	Homozygosity for mutation G212A of the gene for aspartoacylase is associated with atypical form of Canavan's disease. (18070137)	Velinov M.... Wisniewski K.	2008	ASPA
6	Mutational analysis of aspartoacylase: implications for Canavan disease. (17391648)	Hershfield J.R.... Namboodiri M.A.	2007	ASPA
7	Structure of aspartoacylase, the brain enzyme impaired in Canavan disease. (17194761)	Bitto E.... Phillips G.N. Jr.	2007	ASPA
8	Canavan disease or N-acetyl aspartic aciduria: a case report (17196380)	Boughamoura L.... Essoussi A.S.	2007	ASPA
9	Canavan disease: a white matter disorder. (16807907)	Kumar S.... de Vellis J.	2006	ASPA
10	Characterization of human aspartoacylase: the brain enzyme responsible for Canavan disease. (16669630)	Le Coq J.... Viola R.E.	2006	ASPA
11	Canavan disease: studies on the knockout mouse. (16802706)	Matalon R.... Tyring S.K.	2006	ASPA
12	Identification of the zinc binding ligands and the catalytic residue in human aspartoacylase, an enzyme involved in Canavan disease. (17027983)	Herga S.... Giardina T.	2006	ASPA
13	Natural history of Canavan disease revealed by proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted MRI. (17177147)	Janson C.G.... Leone P.	2006	ASPA
14	Canavan disease and the role of N-acetylaspartate in myelin synthesis. (16647192)	Namboodiri A.M.... Madhavarao C.N.	2006	ASPA
15	Rapid detection of three large novel deletions of the aspartoacylase gene in non-Jewish patients with Canavan disease. (16854607)	Zeng B.J.... Kolodny E.H.	2006	ASPA
16	Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease. (15784740)	Madhavarao C.N.... Namboodiri M.A.	2005	ASPA
17	Preimplantation genetic diagnosis of Canavan disease. (16113575)	Yaron Y.... Malcov M.	2005	ASPA
18	Carrier screening for Canavan disease in Australia. (15243987)	Howell V.M.... Burnett L.	2004	ASPA
19	Canavan disease: carrier-frequency determination in the Ashkenazi Jewish population and development of a novel molecular diagnostic assay. (14699612)	Feigenbaum A.... Stockley T.L.	2004	ASPA
20	Canavan disease: a monogenic trait with complex genomic interaction. (14567959)	Surendran S.... Matalon R.	2003	ASPA
21	Molecular basis of Canavan's disease: from human to mouse. (14572138)	Surendran S.... Matalon R.	2003	ASPA
22	Metabolic changes in the knockout mouse for Canavan's disease: implications for patients with Canavan's disease. (14572139)	Surendran S.... Matalon R.	2003	ASPA
23	Two novel aspartoacylase gene (ASPA) missense mutations specific to Norwegian and Swedish patients with Canavan disease. (12205125)	Olsen T.R.... Nilssen O.	2002	ASPA
24	Clinical protocol. Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain. (12162821)	Janson C.... Leone P.	2002	ASPA
25	Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease. (12638939)	Zeng B.J.... Kolodny E.H.	2002	ASPA
26	Knock-out mouse for Canavan disease: a model for gene transfer to the central nervous system. (10894262)	Matalon R.... Szucs S.	2000	ASPA
27	Mutation detection in the aspartoacylase gene in 17 patients with Canavan disease: four new mutations in the non-Jewish population. (10909858)	Sistermans E.A.... van Oost B.A.	2000	ASPA
28	Aspartoacylase gene transfer to the mammalian central nervous system with therapeutic implications for Canavan disease. (10894213)	Leone P.... Bilianuk L.	2000	ASPA
29	Novel splice site mutation of aspartoacylase gene in a Turkish patient with Canavan disease. (10701101)	Rady P.L.... Matalon R.	2000	ASPA
30	The spectrum of mutations of the aspartoacylase gene in Canavan disease in non-Jewish patients. (10407784)	Elpeleg O.N.... Shaag A.	1999	ASPA
31	Novel missense mutation (Y231C) in a Turkish patient with Canavan disease. (10564886)	Rady P.L.... Langenbeck U.	1999	ASPA
32	The clinical course of Canavan disease. (9568915)	Traeger E.C.... Rapin I.	1998	ASPA
33	Use of localized proton nuclear magnetic resonance spectroscopy in Canavan's disease. (10028864)	Aydinli N.... Ozmen M.	1998	ASPA
34	Missense mutation (I143T) in a Japanese patient with Canavan disease. (9452117)	Kobayashi K.... Sakuragawa N.	1998	ASPA
35	Canavan disease: diagnosis and molecular analysis. (10464621)	Matalon R.	1997	ASPA
36	Canavan disease. Analysis of the nature of the metabolic lesions responsible for development of the observed clinical symptoms. (9407392)	Baslow M.H.... Resnik T.R.	1997	ASPA
37	Identification and expression of eight novel mutations among non- Jewish patients with Canavan disease. (8659549)	Kaul R.... Clarke J.T.R.	1996	ASPA
38	Novel (Cys152 > Arg) missense mutation in an Arab patient with Canavan disease. (7599639)	Kaul R.... Matalon R.	1995	ASPA
39	Canavan disease: molecular basis of aspartoacylase deficiency. (7528829)	Kaul R.... Matalon R.	1994	ASPA
40	Canavan disease: mutations among Jewish and non-Jewish patients. (8023850)	Kaul R.... Matalon R.	1994	ASPA
41	Prenatal detection of Canavan disease (aspartoacylase deficiency) by DNA analysis. (7707689)	Elpeleg O.N.... Jakobs C.	1994	ASPA
42	Magnetic resonance imaging in juvenile Canavan disease. (8223809)	Toft P.B.... Hennig J.	1993	ASPA
43	Cranial ultrasound findings in aspartoacylase deficiency (Canavan disease). (8233699)	Buhrer C.... Kaufmann H.J.	1993	ASPA
44	A case of Canavan disease: the first biochemically proven case in a Japanese girl. (8279652)	Hamaguchi H.... Matsumoto I.	1993	ASPA
45	Protracted clinical course for patients with Canavan disease. (8335152)	Zelnik N.... Harel S.	1993	ASPA
46	Canavan disease: biochemical and molecular studies. (8412017)	Matalon R.... Michals K.	1993	ASPA
47	A radiometric assay for aspartoacylase activity in human fibroblasts: application for the diagnosis of Canavan's disease. (1756590)	Barash V.... Gilon C.	1991	ASPA
48	Variable course of Canavan disease in two boys with early infantile aspartoacylase deficiency. (1936635)	von Moers A.... Schutgens R.H.	1991	ASPA
49	Aspartoacylase deficiency and Canavan disease in Saudi Arabia. (2309767)	Ozand P.T.... Dhalla M.	1990	ASPA
50	N-acetylaspartic aciduria in Canavan disease: another proof in two infants. (2234319)	Yalaz K.... Renda Y.	1990	ASPA

Genes related to canavan disease according to GeneCards:

(show all 15)

id	Symbol	Description	Score	GeneCards Section Context
1	ASPA	aspartoacylase	11.1	Aliases & Descriptions, Publications, Summaries
2	NEU1	sialidase 1 (lysosomal sialidase)	11.0
3	FOLH1	folate hydrolase (prostate-specific membrane antigen) 1	11.0
4	BRCA1	breast cancer 1, early onset	11.0
5	MKRN3	makorin ring finger protein 3	11.0	Disorders
6	AKAP5	A kinase (PRKA) anchor protein 5	11.0
7	SLC1A6	solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6	11.0
8	GABRA6	gamma-aminobutyric acid (GABA) A receptor, alpha 6	11.0
9	CACNB3	calcium channel, voltage-dependent, beta 3 subunit	11.0
10	ALDH5A1	aldehyde dehydrogenase 5 family, member A1	11.0	Publications
11	GLUD1	glutamate dehydrogenase 1	11.0	Publications
12	GRIA3	glutamate receptor, ionotropic, AMPA 3	11.0	Publications
13	SLC13A3	solute carrier family 13 (sodium-dependent dicarboxylate transporter), member 3	11.0
14	MID1	midline 1 (Opitz/BBB syndrome)	11.0	Disorders
15	GPT	glutamic-pyruvate transaminase (alanine aminotransferase)	11.0	Publications

Pathways related to canavan disease according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Alanine, aspartate and glutamate metabolism20	8.9	ASPA, GPT, ALDH5A1, GLUD1

Compounds related to canavan disease according to GeneDecks:

(show all 19)

id	Compound	Score	Top Affiliating Genes
1	n-acetyl-aspartyl-glutamate32	10.3	FOLH1, ASPA
2	n-acetylaspartate32	10.2	FOLH1, ASPA
3	vigabatrin32 42 9 9	12.9	ALDH5A1, GLUD1
4	amantadine32 9 9	11.9	GPT, NEU1
5	gamma-hydroxybutyrate32	9.8	ALDH5A1, GLUD1
6	monoethylglycinexylidide32	9.8	GLUD1, GPT
7	pentobarbital32 9 9	11.7	GABRA6, GRIA3
8	isoniazid32 34 9 9	12.6	GPT, NEU1
9	6-phosphogluconate32	9.5	GPT, GLUD1
10	L-Aspartic Acid9 18 9	11.5	ASPA, GLUD1
11	succinate32	9.2	ALDH5A1, GLUD1, SLC13A3
12	nmda32 42	10.1	AKAP5, GLUD1, GRIA3, FOLH1
13	gaba32 42	10.0	GRIA3, ALDH5A1, GLUD1, GABRA6
14	aspartate32	9.0	SLC1A6, GLUD1, GPT, ASPA, FOLH1
15	glutamine32	8.9	BRCA1, GPT, ALDH5A1, GLUD1
16	alpha-ketoglutarate32	8.8	SLC13A3, GLUD1, ALDH5A1, GPT
17	L-Glutamic Acid9 18 9	10.7	FOLH1, GRIA3, GPT, GLUD1, SLC1A6
18	alanine32	8.6	GLUD1, ALDH5A1, GPT, FOLH1, BRCA1
19	glutamate32	7.8	SLC1A6, AKAP5, GLUD1, ALDH5A1, GPT, GRIA3

Cellular components related to canavan disease according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	dendritic shaft	GO:043198	9.7	GRIA3, AKAP5
2	asymmetric synapse	GO:032279	9.4	GRIA3, AKAP5

Biological processes related to canavan disease according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	cellular amino acid biosynthetic process	GO:008652	9.5	GPT, GLUD1
2	synaptic transmission	GO:007268	7.9	GRIA3, ALDH5A1, CACNB3, AKAP5, SLC1A6, GABRA6