MCID: CRB150
MIFTS: 45

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 53 12 49 71
Guanidinoacetate Methyltransferase Deficiency 53 12 72 49 24 55 71 14 69
Gamt Deficiency 53 12 49 24 55 71 13
Creatine Deficiency Syndrome Due to Gamt Deficiency 53 24 71
Deficiency of Guanidinoacetate Methyltransferase 24 28
Language Development Disorders 41 69
Ccds2 53 71
Guanidinoacetate Methyltransferase Deficiency 36
Guanidinoacetate Methyltransferase 13

Characteristics:

Orphanet epidemiological data:

55
guanidinoacetate methyltransferase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy; Age of death: young Adult;

OMIM:

53
Inheritance:
autosomal recessive

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


HPO:

31
cerebral creatine deficiency syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 612736
Disease Ontology 12 DOID:0050799
Orphanet 55 ORPHA382
MESH via Orphanet 42 C537622
UMLS via Orphanet 70 C0574080
ICD10 via Orphanet 33 E72.8
MedGen 39 C0574080
KEGG 36 H00834

Summaries for Cerebral Creatine Deficiency Syndrome 2

NIH Rare Diseases : 49 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 creatine deficiency syndromes and striatonigral degeneration, infantile, and has symptoms including ataxia, seizures and myoclonus. An important gene associated with Cerebral Creatine Deficiency Syndrome 2 is GAMT (Guanidinoacetate N-Methyltransferase), and among its related pathways/superpathways are Glycine, serine and threonine 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.

Genetics Home Reference : 24 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 : 53 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)

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.

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:

53
Neurologic Central Nervous System:
ataxia
progressive extrapyramidal movement disorder
mental retardation
myoclonic jerks
increased deep tendon reflexes
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:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 seizures 31 HP:0001250
3 myoclonus 31 HP:0001336
4 intellectual disability 31 HP:0001249
5 hyperreflexia 31 HP:0001347
6 global developmental delay 31 HP:0001263
7 delayed speech and language development 31 HP:0000750
8 hypertonia 31 HP:0001276
9 infantile muscular hypotonia 31 HP:0008947
10 progressive extrapyramidal movement disorder 31 HP:0007153

UMLS symptoms related to Cerebral Creatine Deficiency Syndrome 2:


myoclonus, ataxia

MGI Mouse Phenotypes related to Cerebral Creatine Deficiency Syndrome 2:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.1 SLC6A6 SLC6A8 GAMT GATM HAPLN1 OAT

Drugs & Therapeutics for Cerebral Creatine Deficiency Syndrome 2

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Creatine Approved, Investigational, Nutraceutical 57-00-1 586

Interventional clinical trials:


# 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:

# Genetic test Affiliating Genes
1 Deficiency of Guanidinoacetate Methyltransferase 28 GAMT

Anatomical Context for Cerebral Creatine Deficiency Syndrome 2

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

38
Brain, Testes

Publications for Cerebral Creatine Deficiency Syndrome 2

Articles related to Cerebral Creatine Deficiency Syndrome 2:

(show all 33)
# Title Authors Year
1
A pilot study to estimate incidence of guanidinoacetate methyltransferase deficiency in newborns by direct sequencing of the GAMT gene. ( 26319512 )
2016
2
Mild guanidinoacetate increase under partial guanidinoacetate methyltransferase deficiency strongly affects brain cell development. ( 25896543 )
2015
3
Carrier frequency of guanidinoacetate methyltransferase deficiency in the general population by functional characterization of missense variants in the GAMT gene. ( 26003046 )
2015
4
A Japanese adult case of guanidinoacetate methyltransferase deficiency. ( 23846910 )
2014
5
Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene. ( 24415674 )
2014
6
Case study for the evaluation of current treatment recommendations of guanidinoacetate methyltransferase deficiency: ineffectiveness of sodium benzoate. ( 24766785 )
2014
7
Epileptic and electroencephalographic manifestations of guanidinoacetate-methyltransferase deficiency. ( 24165373 )
2013
8
Guanidinoacetate methyltransferase deficiency: first steps to newborn screening for a treatable neurometabolic disease. ( 23031365 )
2012
9
Guanidinoacetate methyltransferase deficiency (GAMT). ( 19289269 )
2010
10
Successful treatment of a guanidinoacetate methyltransferase deficient patient: findings with relevance to treatment strategy and pathophysiology. ( 17466557 )
2007
11
Guanidinoacetate methyltransferase deficiency masquerading as a mitochondrial encephalopathy. ( 17171576 )
2007
12
Severe speech delay as the presenting symptom of guanidinoacetate methyltransferase deficiency. ( 17641269 )
2007
13
Prenatal diagnosis of guanidinoacetate methyltransferase deficiency: increased guanidinoacetate concentrations in amniotic fluid. ( 16595836 )
2006
14
Presymptomatic treatment of neonatal guanidinoacetate methyltransferase deficiency. ( 16924036 )
2006
15
Guanidinoacetate methyltransferase deficiency identified in adults and a child with mental retardation. ( 15651030 )
2005
16
Use of denaturing HPLC to provide efficient detection of mutations causing guanidinoacetate methyltransferase deficiency. ( 16054853 )
2005
17
Enzyme assay for diagnosis of guanidinoacetate methyltransferase deficiency. ( 14752017 )
2004
18
Guanidinoacetate methyltransferase deficiency: differences of creatine uptake in human brain and muscle. ( 15234333 )
2004
19
Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies. ( 12324495 )
2002
20
Denaturing gradient gel electrophoresis for the molecular characterization of six patients with guanidinoacetate methyltransferase deficiency. ( 11978605 )
2002
21
Automated high-performance liquid chromatographic method for the determination of guanidinoacetic acid in dried blood spots: a tool for early diagnosis of guanidinoacetate methyltransferase deficiency. ( 11393723 )
2001
22
Improving treatment of guanidinoacetate methyltransferase deficiency: reduction of guanidinoacetic acid in body fluids by arginine restriction and ornithine supplementation. ( 11749046 )
2001
23
Two new severe mutations causing guanidinoacetate methyltransferase deficiency. ( 11136556 )
2000
24
Upregulation of respiratory chain enzymes in guanidinoacetate methyltransferase deficiency. ( 10896298 )
2000
25
Brain creatine depletion: guanidinoacetate methyltransferase deficiency (improving with creatine supplementation). ( 11087795 )
2000
26
An accurate stable isotope dilution gas chromatographic-mass spectrometric approach to the diagnosis of guanidinoacetate methyltransferase deficiency. ( 9919967 )
1998
27
Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. ( 9322805 )
1997
28
Guanidinoacetate methyltransferase deficiency: new clinical features. ( 9367297 )
1997
29
Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: diagnostic tools for a new inborn error of metabolism. ( 9386672 )
1997
30
Guanidinoacetate methyltransferase deficiency: a newly recognized inborn error of creatine biosynthesis. ( 9060147 )
1997
31
Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. ( 8651275 )
1996
32
Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. ( 8813986 )
1996
33
Sakaguchi reaction: a useful method for screening guanidinoacetate-methyltransferase deficiency. ( 8892034 )
1996

Variations for Cerebral Creatine Deficiency Syndrome 2

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

71 (show all 18)
# 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 rs886054247
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
# 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 KEGG:

36
# Name Kegg Source Accession
1 Glycine, serine and threonine metabolism hsa00260
2 Arginine and proline metabolism hsa00330

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

# 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:

# 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:

# 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
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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....