MCID: CRB148
MIFTS: 38

Cerebral Creatine Deficiency Syndrome 3

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

Aliases & Classifications for Cerebral Creatine Deficiency Syndrome 3

MalaCards integrated aliases for Cerebral Creatine Deficiency Syndrome 3:

Name: Cerebral Creatine Deficiency Syndrome 3 53 12 24 71
Agat Deficiency 53 12 24 55 71 13 14
Arginine:glycine Amidinotransferase Deficiency 53 12 24 71 28 69
Creatine Deficiency Syndrome Due to Agat Deficiency 53 24 71
Gatm Deficiency 53 24 71
L-Arginine:glycine Amidinotransferase Deficiency 24 55
Ccds3 53 71
L-Arginine:glycine Aminidotransferase Deficiency 24

Characteristics:

Orphanet epidemiological data:

55
l-arginine:glycine amidinotransferase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
favorable response to oral creatine treatment


HPO:

31
cerebral creatine deficiency syndrome 3:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

OMIM 53 612718
Disease Ontology 12 DOID:0050712
Orphanet 55 ORPHA35704
UMLS via Orphanet 70 C2675179
ICD10 via Orphanet 33 E72.8
MedGen 39 C2675179
UMLS 69 C2675179

Summaries for Cerebral Creatine Deficiency Syndrome 3

OMIM : 53 Cerebral creatine deficiency syndrome-3 is an autosomal recessive disorder characterized by developmental delay/regression, mental retardation, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain (Schulze, 2003). Most patients develop a myopathy characterized by muscle weakness and atrophy later in life. Oral creatine supplementation can offer symptom improvement (summary by Edvardson et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of cerebral creatine deficiency syndrome, see CCDS1 (300352). (612718)

MalaCards based summary : Cerebral Creatine Deficiency Syndrome 3, also known as agat deficiency, is related to l-arginine:glycine amidinotransferase deficiency and encephalomyopathy, and has symptoms including intellectual disability, failure to thrive and global developmental delay. An important gene associated with Cerebral Creatine Deficiency Syndrome 3 is GATM (Glycine Amidinotransferase), and among its related pathways/superpathways are Arginine and proline metabolism and Glycine, serine and threonine metabolism. The drug Creatine has been mentioned in the context of this disorder. Affiliated tissues include brain, and related phenotype is Decreased JFH-1 genotype 2a Hepatitis C virus (HCV) infection.

Disease Ontology : 12 An amino acid metabolic disorder that has material basis in a mutation in the GATM gene resulting in deficiency of arginine:glycine amidinotransferase which then limits creatine synthesis.

Genetics Home Reference : 24 Arginine:glycine amidinotransferase deficiency is an inherited disorder that primarily affects the brain. People with this disorder have mild to moderate intellectual disability and delayed speech development. Some affected individuals develop autistic behaviors that affect communication and social interaction. They may experience seizures, especially when they have a fever.

UniProtKB/Swiss-Prot : 71 Cerebral creatine deficiency syndrome 3: An autosomal recessive disorder characterized by developmental delay/regression, mental retardation, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. Most patients develop a myopathy characterized by muscle weakness and atrophy later in life.

Related Diseases for Cerebral Creatine Deficiency Syndrome 3

Graphical network of the top 20 diseases related to Cerebral Creatine Deficiency Syndrome 3:



Diseases related to Cerebral Creatine Deficiency Syndrome 3

Symptoms & Phenotypes for Cerebral Creatine Deficiency Syndrome 3

Symptoms via clinical synopsis from OMIM:

53
Growth Other:
failure to thrive

Neurologic Central Nervous System:
delayed psychomotor development
mental retardation, mild to moderate
speech delay
brain mrs shows decreased creatine content

Laboratory Abnormalities:
decreased plasma and urinary guanidinoacetate (gaa)
organic aciduria

Muscle Soft Tissue:
muscle weakness, predominantly proximal (in some patients)
gowers sign (in some patients)
muscle biopsy shows fiber type variation (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
autistic behavior


Clinical features from OMIM:

612718

Human phenotypes related to Cerebral Creatine Deficiency Syndrome 3:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 failure to thrive 31 HP:0001508
3 global developmental delay 31 HP:0001263
4 delayed speech and language development 31 HP:0000750
5 autism 31 HP:0000717
6 organic aciduria 31 HP:0001992
7 abnormality of creatine metabolism 31 HP:0012113
8 gowers sign 31 occasional (7.5%) HP:0003391

GenomeRNAi Phenotypes related to Cerebral Creatine Deficiency Syndrome 3 according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased JFH-1 genotype 2a Hepatitis C virus (HCV) infection GR00233-A-1 8.8 DDX21 GATM SLC6A8

Drugs & Therapeutics for Cerebral Creatine Deficiency Syndrome 3

Drugs for Cerebral Creatine Deficiency Syndrome 3 (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 3

Genetic Tests for Cerebral Creatine Deficiency Syndrome 3

Genetic tests related to Cerebral Creatine Deficiency Syndrome 3:

# Genetic test Affiliating Genes
1 Arginine:glycine Amidinotransferase Deficiency 28 GATM

Anatomical Context for Cerebral Creatine Deficiency Syndrome 3

MalaCards organs/tissues related to Cerebral Creatine Deficiency Syndrome 3:

38
Brain

Publications for Cerebral Creatine Deficiency Syndrome 3

Articles related to Cerebral Creatine Deficiency Syndrome 3:

# Title Authors Year
1
Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide. ( 26490222 )
2015
2
Creatine deficiency syndrome. A treatable myopathy due to arginine-glycine amidinotransferase (AGAT) deficiency. ( 23770102 )
2013
3
l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation. ( 20682460 )
2010
4
Arginine:glycine amidinotransferase (AGAT) deficiency in a newborn: early treatment can prevent phenotypic expression of the disease. ( 16769397 )
2006
5
Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree. ( 12468279 )
2002

Variations for Cerebral Creatine Deficiency Syndrome 3

UniProtKB/Swiss-Prot genetic disease variations for Cerebral Creatine Deficiency Syndrome 3:

71 (show all 11)
# Symbol AA change Variation ID SNP ID
1 GATM p.Tyr203Ser VAR_069816 rs397514709
2 GATM p.Arg413Gln VAR_071789
3 GATM p.Arg413Trp VAR_071790
4 GATM p.Pro105Leu VAR_076486 rs147804855
5 GATM p.Glu181Lys VAR_076487 rs376982466
6 GATM p.Ala185Pro VAR_076488
7 GATM p.Arg189Cys VAR_076489 rs377578020
8 GATM p.Ala208Thr VAR_076490 rs374059924
9 GATM p.Arg282His VAR_076493 rs371447931
10 GATM p.Leu329Val VAR_076494 rs373802463
11 GATM p.Pro346Leu VAR_076495 rs142814307

ClinVar genetic disease variations for Cerebral Creatine Deficiency Syndrome 3:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 GATM NM_001482.2(GATM): c.484+1G> T single nucleotide variant Pathogenic rs80338738 GRCh37 Chromosome 15, 45661523: 45661523
2 GATM NM_001482.2(GATM): c.1111dupA (p.Met371Asnfs) duplication Pathogenic rs397515542 GRCh37 Chromosome 15, 45656146: 45656146
3 GATM NM_001482.2(GATM): c.505C> T (p.Arg169Ter) single nucleotide variant Pathogenic rs397514708 GRCh37 Chromosome 15, 45660438: 45660438
4 GATM NM_001482.2(GATM): c.608A> C (p.Tyr203Ser) single nucleotide variant Pathogenic rs397514709 GRCh37 Chromosome 15, 45660335: 45660335
5 GATM NM_001482.2(GATM): c.446G> A (p.Trp149Ter) single nucleotide variant Pathogenic rs80338737 GRCh37 Chromosome 15, 45661562: 45661562

Expression for Cerebral Creatine Deficiency Syndrome 3

Search GEO for disease gene expression data for Cerebral Creatine Deficiency Syndrome 3.

Pathways for Cerebral Creatine Deficiency Syndrome 3

Pathways related to Cerebral Creatine Deficiency Syndrome 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.89 GAMT GATM OAT
2
Show member pathways
10.87 GAMT GATM
3
Show member pathways
10.18 GAMT GATM OAT

GO Terms for Cerebral Creatine Deficiency Syndrome 3

Biological processes related to Cerebral Creatine Deficiency Syndrome 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 muscle contraction GO:0006936 9.16 GAMT SLC6A8
2 creatine biosynthetic process GO:0006601 8.96 GAMT GATM
3 creatine metabolic process GO:0006600 8.8 GAMT GATM SLC6A8

Sources for Cerebral Creatine Deficiency Syndrome 3

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
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