MCID: CRB150
MIFTS: 41

Cerebral Creatine Deficiency Syndrome 2

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Cerebral Creatine Deficiency Syndrome 2

MalaCards integrated aliases for Cerebral Creatine Deficiency Syndrome 2:

Name: Cerebral Creatine Deficiency Syndrome 2 54 12 50 71
Guanidinoacetate Methyltransferase Deficiency 12 50 24 25 56 71 14 69
Gamt Deficiency 12 50 24 25 56 71 13
Creatine Deficiency Syndrome Due to Gamt Deficiency 25 71
Deficiency of Guanidinoacetate Methyltransferase 25 29
Language Development Disorders 42 69
Guanidinoacetate Methyltransferase 13
Ccds2 71

Characteristics:

Orphanet epidemiological data:

56
guanidinoacetate methyltransferase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy; Age of death: young Adult;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
clinical and biochemical symptoms improved with oral administration of creatine monohydrate


HPO:

32
cerebral creatine deficiency syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Cerebral Creatine Deficiency Syndrome 2

NIH Rare Diseases : 50 guanidinoacetate methyltransferase (gamt) deficiency is an inherited disease that affects the brain and muscles. people with this disease may begin showing symptoms from early infancy to age three. signs and symptoms can vary but may include mild to severe intellectual disability, recurrent seizures (epilepsy), problems with speech, and involuntary movements. people with this disease may also have behavioral problems, including hyperactivity, autistic behaviors, and self-mutilation. gamt deficiency is caused by changes (mutations) in the gamt gene. the disease is inherited in an autosomal recessive manner. diagnosis of the disease may be based on finding increased levels of guanidinoacetate in the urine, and the diagnosis can be confirmed with genetic testing. treatment for the disease aims to increase the levels of creatine in the brain through supplementation with high doses of oral creatine monohydrate. last updated: 7/11/2017

MalaCards based summary : Cerebral Creatine Deficiency Syndrome 2, also known as guanidinoacetate methyltransferase deficiency, is related to striatonigral degeneration, infantile and homocystinuria, and has symptoms including myoclonus, ataxia and hyperreflexia. An important gene associated with Cerebral Creatine Deficiency Syndrome 2 is GAMT (Guanidinoacetate N-Methyltransferase), and among its related pathways/superpathways are Amino Acid metabolism and Arginine and proline metabolism. The drug Creatine has been mentioned in the context of this disorder. Affiliated tissues include brain and testes, and related phenotype is behavior/neurological.

UniProtKB/Swiss-Prot : 71 Cerebral creatine deficiency syndrome 2: An autosomal recessive disorder characterized by developmental delay and regression, mental retardation, severe disturbance of expressive and cognitive speech, intractable seizures, movement disturbances, severe depletion of creatine and phosphocreatine in the brain, and accumulation of guanidinoacetic acid in brain and body fluids.

Genetics Home Reference : 25 Guanidinoacetate methyltransferase deficiency is an inherited disorder that primarily affects the brain and muscles. Without early treatment, people with this disorder have neurological problems that are usually severe. These problems include intellectual disability, speech development limited to a few words, and recurrent seizures (epilepsy). Affected individuals may also exhibit autistic behaviors that affect communication and social interaction or self-injurious behaviors such as head-banging. Other features of this disorder can include involuntary movements (extrapyramidal dysfunction) such as tremors or facial tics.

OMIM : 54
Guanidinoacetate methyltransferase deficiency, an autosomal recessive inborn error of creatine synthesis, is characterized by developmental delay/regression, mental retardation, severe disturbance of expressive and cognitive speech, intractable seizures and movement disturbances, severe depletion of creatine/phosphocreatine in the brain, and accumulation of guanidinoacetic acid (GAA) in brain and body fluids (summary by Schulze, 2003). For a general phenotypic description and a discussion of genetic heterogeneity of CCDS, see CCDS1 (300352). (612736)

Wikipedia : 72 Guanidinoacetate methyltransferase deficiency, also called GAMT deficiency, is an autosomal... more...

Related Diseases for Cerebral Creatine Deficiency Syndrome 2

Graphical network of the top 20 diseases related to Cerebral Creatine Deficiency Syndrome 2:



Diseases related to Cerebral Creatine Deficiency Syndrome 2

Symptoms & Phenotypes for Cerebral Creatine Deficiency Syndrome 2

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
mental retardation
ataxia
seizures, intractable
increased deep tendon reflexes
myoclonic jerks
more
Laboratory- Abnormalities:
extremely low creatine excretion
low csf creatine
low csf creatinine
deficiency of creatine phosphate in brain
accumulation of guanidinoacetate in brain
more
Muscle Soft Tissue:
hypotonia in infancy


Clinical features from OMIM:

612736

Human phenotypes related to Cerebral Creatine Deficiency Syndrome 2:

32 (show all 10)
id Description HPO Frequency HPO Source Accession
1 myoclonus 32 HP:0001336
2 ataxia 32 HP:0001251
3 hyperreflexia 32 HP:0001347
4 seizures 32 HP:0001250
5 hypertonia 32 HP:0001276
6 global developmental delay 32 HP:0001263
7 intellectual disability 32 HP:0001249
8 delayed speech and language development 32 HP:0000750
9 progressive extrapyramidal movement disorder 32 HP:0007153
10 infantile muscular hypotonia 32 HP:0008947

UMLS symptoms related to Cerebral Creatine Deficiency Syndrome 2:


ataxia, myoclonus

MGI Mouse Phenotypes related to Cerebral Creatine Deficiency Syndrome 2:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.02 GAMT GATM OAT SLC6A6 SLC6A8

Drugs & Therapeutics for Cerebral Creatine Deficiency Syndrome 2

Drugs for Cerebral Creatine Deficiency Syndrome 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Creatine Nutraceutical 57-00-1 586

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Biomarker for Creatine Deficiency Syndromes Recruiting NCT02934854

Search NIH Clinical Center for Cerebral Creatine Deficiency Syndrome 2

Cochrane evidence based reviews: language development disorders

Genetic Tests for Cerebral Creatine Deficiency Syndrome 2

Genetic tests related to Cerebral Creatine Deficiency Syndrome 2:

id Genetic test Affiliating Genes
1 Deficiency of Guanidinoacetate Methyltransferase 29
2 Guanidinoacetate Methyltransferase Deficiency 24 GAMT

Anatomical Context for Cerebral Creatine Deficiency Syndrome 2

MalaCards organs/tissues related to Cerebral Creatine Deficiency Syndrome 2:

39
Brain, Testes

Publications for Cerebral Creatine Deficiency Syndrome 2

Variations for Cerebral Creatine Deficiency Syndrome 2

UniProtKB/Swiss-Prot genetic disease variations for Cerebral Creatine Deficiency Syndrome 2:

71 (show all 18)
id Symbol AA change Variation ID SNP ID
1 GAMT p.Trp20Ser VAR_058102 rs80338734
2 GAMT p.Met50Leu VAR_058103 rs104894694
3 GAMT p.His51Pro VAR_058104
4 GAMT p.Ala54Pro VAR_058105
5 GAMT p.Cys169Tyr VAR_058106 rs121909272
6 GAMT p.Leu197Pro VAR_058107
7 GAMT p.Trp45Arg VAR_071777
8 GAMT p.Gly68Cys VAR_071778
9 GAMT p.Ala75Val VAR_071779
10 GAMT p.Val78Glu VAR_071780
11 GAMT p.Val110Phe VAR_071781 rs753198836
12 GAMT p.Asp135Asn VAR_071782 rs774144200
13 GAMT p.His147Tyr VAR_071783
14 GAMT p.Leu159Pro VAR_071784
15 GAMT p.Gly164Asp VAR_071785 rs760101382
16 GAMT p.Leu166Pro VAR_071786
17 GAMT p.Cys169Arg VAR_071787
18 GAMT p.Arg208Pro VAR_071788 rs767887772

ClinVar genetic disease variations for Cerebral Creatine Deficiency Syndrome 2:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 GAMT GAMT, IVS2DS, G-A, -1 single nucleotide variant Pathogenic
2 GAMT NM_000156.5(GAMT): c.299_311dupGGGACTGGGCCCC (p.Arg105Glyfs) duplication Pathogenic rs80338736 GRCh37 Chromosome 19, 1399810: 1399822
3 GAMT NM_000156.5(GAMT): c.59G> C (p.Trp20Ser) single nucleotide variant Pathogenic rs80338734 GRCh37 Chromosome 19, 1401417: 1401417
4 GAMT NM_000156.5(GAMT): c.506G> A (p.Cys169Tyr) single nucleotide variant Pathogenic rs121909272 GRCh37 Chromosome 19, 1398979: 1398979
5 GAMT NM_000156.5(GAMT): c.148A> C (p.Met50Leu) single nucleotide variant Pathogenic rs104894694 GRCh37 Chromosome 19, 1401328: 1401328
6 GAMT NM_000156.5(GAMT): c.327G> A (p.Lys109=) single nucleotide variant Pathogenic rs80338735 GRCh37 Chromosome 19, 1399792: 1399792
7 GAMT NM_000156.5(GAMT): c.522G> A (p.Trp174Ter) single nucleotide variant Pathogenic rs370421531 GRCh38 Chromosome 19, 1398964: 1398964
8 GAMT NM_000156.5(GAMT): c.419C> A (p.Ser140Ter) single nucleotide variant Likely pathogenic rs747656257 GRCh37 Chromosome 19, 1399167: 1399167
9 GAMT NM_000156.5(GAMT): c.133T> A (p.Trp45Arg) single nucleotide variant Likely pathogenic rs886054247 GRCh37 Chromosome 19, 1401343: 1401343

Expression for Cerebral Creatine Deficiency Syndrome 2

Search GEO for disease gene expression data for Cerebral Creatine Deficiency Syndrome 2.

Pathways for Cerebral Creatine Deficiency Syndrome 2

Pathways related to Cerebral Creatine Deficiency Syndrome 2 according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 11.29 ARG1 CS OAT
2
Show member pathways
11.01 ARG1 GAMT GATM OAT
3
Show member pathways
10.97 GAMT GATM
4
Show member pathways
10.3 ARG1 GAMT GATM OAT

GO Terms for Cerebral Creatine Deficiency Syndrome 2

Biological processes related to Cerebral Creatine Deficiency Syndrome 2 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 neurotransmitter transport GO:0006836 9.16 SLC6A6 SLC6A8
2 creatine biosynthetic process GO:0006601 8.96 GAMT GATM
3 creatine metabolic process GO:0006600 8.8 GAMT GATM SLC6A8

Molecular functions related to Cerebral Creatine Deficiency Syndrome 2 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 neurotransmitter:sodium symporter activity GO:0005328 8.62 SLC6A6 SLC6A8

Sources for Cerebral Creatine Deficiency Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....