CCDS3
MCID: CRB148
MIFTS: 40

Cerebral Creatine Deficiency Syndrome 3 (CCDS3)

Categories: Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Oral 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 58 12 26 76
Arginine:glycine Amidinotransferase Deficiency 58 12 26 76 30 6 74
Agat Deficiency 58 12 26 60 76 13 15
Creatine Deficiency Syndrome Due to Agat Deficiency 58 26 76
Gatm Deficiency 58 26 76
L-Arginine:glycine Amidinotransferase Deficiency 26 60
Ccds3 58 76
Deficiency, Cerebral Creatine, Syndrome, Type 3 ) 41
L-Arginine:glycine Aminidotransferase Deficiency 26

Characteristics:

Orphanet epidemiological data:

60
l-arginine:glycine amidinotransferase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
favorable response to oral creatine treatment


HPO:

33
cerebral creatine deficiency syndrome 3:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0050712
OMIM 58 612718
ICD10 via Orphanet 35 E72.8
UMLS via Orphanet 75 C2675179
Orphanet 60 ORPHA35704
MedGen 43 C2675179
UMLS 74 C2675179

Summaries for Cerebral Creatine Deficiency Syndrome 3

OMIM : 58 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 myopathy. 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 drugs Creatine and Glycine have been mentioned in the context of this disorder. Affiliated tissues include brain, and related phenotypes are gowers sign and intellectual disability

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 : 26 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 : 76 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.

Wikipedia : 77 Arginine:glycine amidinotransferase deficiency (AGAT deficiency) is an autosomal recessive cerebral... more...

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

Human phenotypes related to Cerebral Creatine Deficiency Syndrome 3:

33 (show all 8)
# Description HPO Frequency HPO Source Accession
1 gowers sign 33 occasional (7.5%) HP:0003391
2 intellectual disability 33 HP:0001249
3 failure to thrive 33 HP:0001508
4 global developmental delay 33 HP:0001263
5 delayed speech and language development 33 HP:0000750
6 autism 33 HP:0000717
7 organic aciduria 33 HP:0001992
8 reduced brain creatine level by mrs 33 HP:0025051

Symptoms via clinical synopsis from OMIM:

58
Growth Other:
failure to thrive

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

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

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

Clinical features from OMIM:

612718

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

27
# 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:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.35 GAMT GATM HAPLN1 OAT SLC6A8
2 renal/urinary system MP:0005367 8.92 GAMT GATM 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
2
Glycine Approved, Nutraceutical, Vet_approved 56-40-6 750
3 arginine

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 30 GATM

Anatomical Context for Cerebral Creatine Deficiency Syndrome 3

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

42
Brain

Publications for Cerebral Creatine Deficiency Syndrome 3

Articles related to Cerebral Creatine Deficiency Syndrome 3:

# Title Authors Year
1
Fifteen-year follow-up of Italian families affected by arginine glycine amidinotransferase deficiency. ( 28148286 )
2017
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
Diagnostic enzyme assay that uses stable-isotope-labeled substrates to detect L-arginine:glycine amidinotransferase deficiency. ( 12709373 )
2003
6
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:

76 (show all 11)
# Symbol AA change Variation ID SNP ID
1 GATM p.Tyr203Ser VAR_069816 rs397514709
2 GATM p.Arg413Gln VAR_071789 rs146165321
3 GATM p.Arg413Trp VAR_071790 rs124482480
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 108)
# Gene Variation Type Significance SNP ID Assembly Location
1 GATM NM_001482.2(GATM): c.701A> G (p.Asp234Gly) single nucleotide variant Uncertain significance rs146057680 GRCh38 Chromosome 15, 45366483: 45366483
2 GATM NM_001482.2(GATM): c.701A> G (p.Asp234Gly) single nucleotide variant Uncertain significance rs146057680 GRCh37 Chromosome 15, 45658681: 45658681
3 GATM NM_001482.2(GATM): c.407C> T (p.Thr136Met) single nucleotide variant Conflicting interpretations of pathogenicity rs148564534 GRCh37 Chromosome 15, 45661601: 45661601
4 GATM NM_001482.2(GATM): c.407C> T (p.Thr136Met) single nucleotide variant Conflicting interpretations of pathogenicity rs148564534 GRCh38 Chromosome 15, 45369403: 45369403
5 GATM NM_001482.2(GATM): c.446G> A (p.Trp149Ter) single nucleotide variant Pathogenic rs80338737 GRCh37 Chromosome 15, 45661562: 45661562
6 GATM NM_001482.2(GATM): c.446G> A (p.Trp149Ter) single nucleotide variant Pathogenic rs80338737 GRCh38 Chromosome 15, 45369364: 45369364
7 GATM NM_001482.2(GATM): c.484+1G> T single nucleotide variant Pathogenic rs80338738 GRCh37 Chromosome 15, 45661523: 45661523
8 GATM NM_001482.2(GATM): c.484+1G> T single nucleotide variant Pathogenic rs80338738 GRCh38 Chromosome 15, 45369325: 45369325
9 GATM NM_001482.2(GATM): c.1111dupA (p.Met371Asnfs) duplication Pathogenic rs397515542 GRCh37 Chromosome 15, 45656146: 45656146
10 GATM NM_001482.2(GATM): c.1111dupA (p.Met371Asnfs) duplication Pathogenic rs397515542 GRCh38 Chromosome 15, 45363948: 45363948
11 GATM NM_001482.2(GATM): c.505C> T (p.Arg169Ter) single nucleotide variant Pathogenic rs397514708 GRCh37 Chromosome 15, 45660438: 45660438
12 GATM NM_001482.2(GATM): c.505C> T (p.Arg169Ter) single nucleotide variant Pathogenic rs397514708 GRCh38 Chromosome 15, 45368240: 45368240
13 GATM NM_001482.2(GATM): c.608A> C (p.Tyr203Ser) single nucleotide variant Pathogenic rs397514709 GRCh37 Chromosome 15, 45660335: 45660335
14 GATM NM_001482.2(GATM): c.608A> C (p.Tyr203Ser) single nucleotide variant Pathogenic rs397514709 GRCh38 Chromosome 15, 45368137: 45368137
15 GATM NM_001482.2(GATM): c.1252T> C (p.Leu418=) single nucleotide variant Benign rs1145086 GRCh37 Chromosome 15, 45654327: 45654327
16 GATM NM_001482.2(GATM): c.1252T> C (p.Leu418=) single nucleotide variant Benign rs1145086 GRCh38 Chromosome 15, 45362129: 45362129
17 GATM NM_001482.2(GATM): c.330A> T (p.Gln110His) single nucleotide variant Benign rs1288775 GRCh37 Chromosome 15, 45661678: 45661678
18 GATM NM_001482.2(GATM): c.330A> T (p.Gln110His) single nucleotide variant Benign rs1288775 GRCh38 Chromosome 15, 45369480: 45369480
19 GATM NM_001482.2(GATM): c.669T> C (p.Tyr223=) single nucleotide variant Conflicting interpretations of pathogenicity rs151231277 GRCh38 Chromosome 15, 45368076: 45368076
20 GATM NM_001482.2(GATM): c.669T> C (p.Tyr223=) single nucleotide variant Conflicting interpretations of pathogenicity rs151231277 GRCh37 Chromosome 15, 45660274: 45660274
21 GATM NM_001482.2(GATM): c.1041C> T (p.Asp347=) single nucleotide variant Conflicting interpretations of pathogenicity rs139599307 GRCh38 Chromosome 15, 45364798: 45364798
22 GATM NM_001482.2(GATM): c.1041C> T (p.Asp347=) single nucleotide variant Conflicting interpretations of pathogenicity rs139599307 GRCh37 Chromosome 15, 45656996: 45656996
23 GATM NM_001482.2(GATM): c.1239G> A (p.Arg413=) single nucleotide variant Benign/Likely benign rs550159982 GRCh38 Chromosome 15, 45362142: 45362142
24 GATM NM_001482.2(GATM): c.1239G> A (p.Arg413=) single nucleotide variant Benign/Likely benign rs550159982 GRCh37 Chromosome 15, 45654340: 45654340
25 GATM NM_001482.2(GATM): c.-30T> G single nucleotide variant Benign rs8024550 GRCh38 Chromosome 15, 45378483: 45378483
26 GATM NM_001482.2(GATM): c.-30T> G single nucleotide variant Benign rs8024550 GRCh37 Chromosome 15, 45670681: 45670681
27 GATM NM_001482.2(GATM): c.69+13C> T single nucleotide variant Conflicting interpretations of pathogenicity rs573273215 GRCh38 Chromosome 15, 45378372: 45378372
28 GATM NM_001482.2(GATM): c.69+13C> T single nucleotide variant Conflicting interpretations of pathogenicity rs573273215 GRCh37 Chromosome 15, 45670570: 45670570
29 GATM NM_001482.2(GATM): c.845G> A (p.Arg282His) single nucleotide variant Uncertain significance rs371447931 GRCh37 Chromosome 15, 45658377: 45658377
30 GATM NM_001482.2(GATM): c.845G> A (p.Arg282His) single nucleotide variant Uncertain significance rs371447931 GRCh38 Chromosome 15, 45366179: 45366179
31 GATM NM_001482.2(GATM): c.*734_*735insCA insertion Benign rs35410548 GRCh38 Chromosome 15, 45361374: 45361375
32 GATM NM_001482.2(GATM): c.*734_*735insCA insertion Benign rs35410548 GRCh37 Chromosome 15, 45653572: 45653573
33 GATM NM_001482.2(GATM): c.1159G> C (p.Gly387Arg) single nucleotide variant Uncertain significance rs886051202 GRCh38 Chromosome 15, 45363900: 45363900
34 GATM NM_001482.2(GATM): c.1159G> C (p.Gly387Arg) single nucleotide variant Uncertain significance rs886051202 GRCh37 Chromosome 15, 45656098: 45656098
35 GATM NM_001482.2(GATM): c.*715T> C single nucleotide variant Benign rs1049508 GRCh38 Chromosome 15, 45361394: 45361394
36 GATM NM_001482.2(GATM): c.*715T> C single nucleotide variant Benign rs1049508 GRCh37 Chromosome 15, 45653592: 45653592
37 GATM NM_001482.2(GATM): c.*699A> C single nucleotide variant Uncertain significance rs750817737 GRCh38 Chromosome 15, 45361410: 45361410
38 GATM NM_001482.2(GATM): c.*699A> C single nucleotide variant Uncertain significance rs750817737 GRCh37 Chromosome 15, 45653608: 45653608
39 GATM NM_001482.2(GATM): c.*104A> G single nucleotide variant Uncertain significance rs886051201 GRCh38 Chromosome 15, 45362005: 45362005
40 GATM NM_001482.2(GATM): c.*104A> G single nucleotide variant Uncertain significance rs886051201 GRCh37 Chromosome 15, 45654203: 45654203
41 GATM NM_001482.2(GATM): c.*27C> G single nucleotide variant Uncertain significance rs200143728 GRCh38 Chromosome 15, 45362082: 45362082
42 GATM NM_001482.2(GATM): c.*27C> G single nucleotide variant Uncertain significance rs200143728 GRCh37 Chromosome 15, 45654280: 45654280
43 GATM NM_001482.2(GATM): c.222C> T (p.Pro74=) single nucleotide variant Uncertain significance rs774485349 GRCh38 Chromosome 15, 45376667: 45376667
44 GATM NM_001482.2(GATM): c.222C> T (p.Pro74=) single nucleotide variant Uncertain significance rs774485349 GRCh37 Chromosome 15, 45668865: 45668865
45 GATM NM_001482.2(GATM): c.*913G> A single nucleotide variant Likely benign rs17618637 GRCh38 Chromosome 15, 45361196: 45361196
46 GATM NM_001482.2(GATM): c.*913G> A single nucleotide variant Likely benign rs17618637 GRCh37 Chromosome 15, 45653394: 45653394
47 GATM NM_001482.2(GATM): c.*847G> A single nucleotide variant Uncertain significance rs1145087 GRCh38 Chromosome 15, 45361262: 45361262
48 GATM NM_001482.2(GATM): c.*847G> A single nucleotide variant Uncertain significance rs1145087 GRCh37 Chromosome 15, 45653460: 45653460
49 GATM NM_001482.2(GATM): c.*595C> A single nucleotide variant Likely benign rs75565512 GRCh38 Chromosome 15, 45361514: 45361514
50 GATM NM_001482.2(GATM): c.*595C> A single nucleotide variant Likely benign rs75565512 GRCh37 Chromosome 15, 45653712: 45653712

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 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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