MCID: CRB148
MIFTS: 39

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 57 12 25 75
Arginine:glycine Amidinotransferase Deficiency 57 12 25 75 29 6 73
Agat Deficiency 57 12 25 59 75 13 15
Creatine Deficiency Syndrome Due to Agat Deficiency 57 25 75
Gatm Deficiency 57 25 75
L-Arginine:glycine Amidinotransferase Deficiency 25 59
Ccds3 57 75
Deficiency, Cerebral Creatine, Syndrome, Type 3 ) 40
L-Arginine:glycine Aminidotransferase Deficiency 25

Characteristics:

Orphanet epidemiological data:

59
l-arginine:glycine amidinotransferase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
favorable response to oral creatine treatment


HPO:

32
cerebral creatine deficiency syndrome 3:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

OMIM 57 612718
Disease Ontology 12 DOID:0050712
Orphanet 59 ORPHA35704
UMLS via Orphanet 74 C2675179
ICD10 via Orphanet 34 E72.8
MedGen 42 C2675179
UMLS 73 C2675179

Summaries for Cerebral Creatine Deficiency Syndrome 3

OMIM : 57 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 arginine:glycine amidinotransferase deficiency, is related to l-arginine:glycine amidinotransferase deficiency and encephalomyopathy. 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 phenotypes are autism and delayed speech and language development

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 : 25 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 : 75 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:

57
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:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 autism 32 HP:0000717
2 delayed speech and language development 32 HP:0000750
3 intellectual disability 32 HP:0001249
4 global developmental delay 32 HP:0001263
5 failure to thrive 32 HP:0001508
6 organic aciduria 32 HP:0001992
7 gowers sign 32 occasional (7.5%) HP:0003391
8 abnormality of creatine metabolism 32 HP:0012113

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

26
# 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

MGI Mouse Phenotypes related to Cerebral Creatine Deficiency Syndrome 3:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.02 GAMT GATM HAPLN1 OAT 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 Terminated 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 29 GATM

Anatomical Context for Cerebral Creatine Deficiency Syndrome 3

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

41
Brain

Publications for Cerebral Creatine Deficiency Syndrome 3

Articles related to Cerebral Creatine Deficiency Syndrome 3:

# Title Authors Year
1
Arginine-Glycine Amidinotransferase Deficiency and Functional Characterization of Missense Variants in GATM. ( 27233232 )
2016
2
L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome. ( 23026748 )
2013
3
Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency. ( 22386973 )
2012
4
Arginine:glycine amidinotransferase deficiency: a treatable metabolic encephalomyopathy. ( 20625172 )
2010
5
Gas chromatography/mass spectrometry assay for arginine: glycine-amidinotransferase deficiency. ( 15978539 )
2005
6
Diagnostic enzyme assay that uses stable-isotope-labeled substrates to detect L-arginine:glycine amidinotransferase deficiency. ( 12709373 )
2003
7
Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. ( 11555793 )
2001

Variations for Cerebral Creatine Deficiency Syndrome 3

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

75 (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
(show top 50) (show all 76)
# Gene Variation Type Significance SNP ID Assembly Location
1 GATM NM_001482.2(GATM): c.446G> A (p.Trp149Ter) single nucleotide variant Pathogenic rs80338737 GRCh37 Chromosome 15, 45661562: 45661562
2 GATM NM_001482.2(GATM): c.446G> A (p.Trp149Ter) single nucleotide variant Pathogenic rs80338737 GRCh38 Chromosome 15, 45369364: 45369364
3 GATM NM_001482.2(GATM): c.484+1G> T single nucleotide variant Pathogenic rs80338738 GRCh37 Chromosome 15, 45661523: 45661523
4 GATM NM_001482.2(GATM): c.484+1G> T single nucleotide variant Pathogenic rs80338738 GRCh38 Chromosome 15, 45369325: 45369325
5 GATM NM_001482.2(GATM): c.1111dupA (p.Met371Asnfs) duplication Pathogenic rs397515542 GRCh37 Chromosome 15, 45656146: 45656146
6 GATM NM_001482.2(GATM): c.1111dupA (p.Met371Asnfs) duplication Pathogenic rs397515542 GRCh38 Chromosome 15, 45363948: 45363948
7 GATM NM_001482.2(GATM): c.505C> T (p.Arg169Ter) single nucleotide variant Pathogenic rs397514708 GRCh37 Chromosome 15, 45660438: 45660438
8 GATM NM_001482.2(GATM): c.505C> T (p.Arg169Ter) single nucleotide variant Pathogenic rs397514708 GRCh38 Chromosome 15, 45368240: 45368240
9 GATM NM_001482.2(GATM): c.608A> C (p.Tyr203Ser) single nucleotide variant Pathogenic rs397514709 GRCh37 Chromosome 15, 45660335: 45660335
10 GATM NM_001482.2(GATM): c.608A> C (p.Tyr203Ser) single nucleotide variant Pathogenic rs397514709 GRCh38 Chromosome 15, 45368137: 45368137
11 GATM NM_001482.2(GATM): c.407C> T (p.Thr136Met) single nucleotide variant Conflicting interpretations of pathogenicity rs148564534 GRCh37 Chromosome 15, 45661601: 45661601
12 GATM NM_001482.2(GATM): c.407C> T (p.Thr136Met) single nucleotide variant Conflicting interpretations of pathogenicity rs148564534 GRCh38 Chromosome 15, 45369403: 45369403
13 GATM NM_001482.2(GATM): c.845G> A (p.Arg282His) single nucleotide variant Uncertain significance rs371447931 GRCh37 Chromosome 15, 45658377: 45658377
14 GATM NM_001482.2(GATM): c.845G> A (p.Arg282His) single nucleotide variant Uncertain significance rs371447931 GRCh38 Chromosome 15, 45366179: 45366179
15 GATM NM_001482.2(GATM): c.*734_*735insCA insertion Benign rs35410548 GRCh38 Chromosome 15, 45361374: 45361375
16 GATM NM_001482.2(GATM): c.*734_*735insCA insertion Benign rs35410548 GRCh37 Chromosome 15, 45653572: 45653573
17 GATM NM_001482.2(GATM): c.1159G> C (p.Gly387Arg) single nucleotide variant Uncertain significance rs886051202 GRCh38 Chromosome 15, 45363900: 45363900
18 GATM NM_001482.2(GATM): c.1159G> C (p.Gly387Arg) single nucleotide variant Uncertain significance rs886051202 GRCh37 Chromosome 15, 45656098: 45656098
19 GATM NM_001482.2(GATM): c.*715T> C single nucleotide variant Benign rs1049508 GRCh37 Chromosome 15, 45653592: 45653592
20 GATM NM_001482.2(GATM): c.*715T> C single nucleotide variant Benign rs1049508 GRCh38 Chromosome 15, 45361394: 45361394
21 GATM NM_001482.2(GATM): c.*699A> C single nucleotide variant Uncertain significance rs750817737 GRCh38 Chromosome 15, 45361410: 45361410
22 GATM NM_001482.2(GATM): c.*699A> C single nucleotide variant Uncertain significance rs750817737 GRCh37 Chromosome 15, 45653608: 45653608
23 GATM NM_001482.2(GATM): c.*104A> G single nucleotide variant Uncertain significance rs886051201 GRCh38 Chromosome 15, 45362005: 45362005
24 GATM NM_001482.2(GATM): c.*104A> G single nucleotide variant Uncertain significance rs886051201 GRCh37 Chromosome 15, 45654203: 45654203
25 GATM NM_001482.2(GATM): c.*27C> G single nucleotide variant Uncertain significance rs200143728 GRCh38 Chromosome 15, 45362082: 45362082
26 GATM NM_001482.2(GATM): c.*27C> G single nucleotide variant Uncertain significance rs200143728 GRCh37 Chromosome 15, 45654280: 45654280
27 GATM NM_001482.2(GATM): c.222C> T (p.Pro74=) single nucleotide variant Uncertain significance rs774485349 GRCh38 Chromosome 15, 45376667: 45376667
28 GATM NM_001482.2(GATM): c.222C> T (p.Pro74=) single nucleotide variant Uncertain significance rs774485349 GRCh37 Chromosome 15, 45668865: 45668865
29 GATM NM_001482.2(GATM): c.*913G> A single nucleotide variant Likely benign rs17618637 GRCh38 Chromosome 15, 45361196: 45361196
30 GATM NM_001482.2(GATM): c.*913G> A single nucleotide variant Likely benign rs17618637 GRCh37 Chromosome 15, 45653394: 45653394
31 GATM NM_001482.2(GATM): c.*847G> A single nucleotide variant Uncertain significance rs1145087 GRCh38 Chromosome 15, 45361262: 45361262
32 GATM NM_001482.2(GATM): c.*847G> A single nucleotide variant Uncertain significance rs1145087 GRCh37 Chromosome 15, 45653460: 45653460
33 GATM NM_001482.2(GATM): c.*595C> A single nucleotide variant Likely benign rs75565512 GRCh38 Chromosome 15, 45361514: 45361514
34 GATM NM_001482.2(GATM): c.*595C> A single nucleotide variant Likely benign rs75565512 GRCh37 Chromosome 15, 45653712: 45653712
35 GATM NM_001482.2(GATM): c.-72C> T single nucleotide variant Uncertain significance rs886051203 GRCh38 Chromosome 15, 45378525: 45378525
36 GATM NM_001482.2(GATM): c.-72C> T single nucleotide variant Uncertain significance rs886051203 GRCh37 Chromosome 15, 45670723: 45670723
37 GATM NM_001482.2(GATM): c.*940C> T single nucleotide variant Benign rs1049518 GRCh38 Chromosome 15, 45361169: 45361169
38 GATM NM_001482.2(GATM): c.*940C> T single nucleotide variant Benign rs1049518 GRCh37 Chromosome 15, 45653367: 45653367
39 GATM NM_001482.2(GATM): c.*600A> G single nucleotide variant Benign rs1049503 GRCh38 Chromosome 15, 45361509: 45361509
40 GATM NM_001482.2(GATM): c.*600A> G single nucleotide variant Benign rs1049503 GRCh37 Chromosome 15, 45653707: 45653707
41 GATM NM_001482.2(GATM): c.1159+14A> G single nucleotide variant Conflicting interpretations of pathogenicity rs368974196 GRCh38 Chromosome 15, 45363886: 45363886
42 GATM NM_001482.2(GATM): c.1159+14A> G single nucleotide variant Conflicting interpretations of pathogenicity rs368974196 GRCh37 Chromosome 15, 45656084: 45656084
43 GATM NM_001482.2(GATM): c.-171T> C single nucleotide variant Uncertain significance rs886051204 GRCh38 Chromosome 15, 45378624: 45378624
44 GATM NM_001482.2(GATM): c.-171T> C single nucleotide variant Uncertain significance rs886051204 GRCh37 Chromosome 15, 45670822: 45670822
45 GATM NM_001482.2(GATM): c.-200C> T single nucleotide variant Benign rs7164139 GRCh38 Chromosome 15, 45378653: 45378653
46 GATM NM_001482.2(GATM): c.-200C> T single nucleotide variant Benign rs7164139 GRCh37 Chromosome 15, 45670851: 45670851
47 GATM NM_001482.2(GATM): c.-274C> T single nucleotide variant Uncertain significance rs745765661 GRCh38 Chromosome 15, 45378727: 45378727
48 GATM NM_001482.2(GATM): c.-274C> T single nucleotide variant Uncertain significance rs745765661 GRCh37 Chromosome 15, 45670925: 45670925
49 GATM NM_001482.2(GATM): c.387A> T (p.Glu129Asp) single nucleotide variant Uncertain significance rs756420233 GRCh38 Chromosome 15, 45369423: 45369423
50 GATM NM_001482.2(GATM): c.387A> T (p.Glu129Asp) single nucleotide variant Uncertain significance rs756420233 GRCh37 Chromosome 15, 45661621: 45661621

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
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....