CCDS3
MCID: CRB148
MIFTS: 43

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 56 12 25 73
Arginine:glycine Amidinotransferase Deficiency 56 12 25 73 29 6 71
Agat Deficiency 56 12 25 58 73 13 15
Creatine Deficiency Syndrome Due to Agat Deficiency 56 25 73
Gatm Deficiency 56 25 73
L-Arginine:glycine Amidinotransferase Deficiency 25 58
Ccds3 56 73
L-Arginine:glycine Aminidotransferase Deficiency 25
Deficiency, Cerebral Creatine, Syndrome, Type 3 39

Characteristics:

Orphanet epidemiological data:

58
l-arginine:glycine amidinotransferase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;

OMIM:

56
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:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0050712
OMIM 56 612718
OMIM Phenotypic Series 56 PS300352
ICD10 via Orphanet 33 E72.8
UMLS via Orphanet 72 C2675179
Orphanet 58 ORPHA35704
MedGen 41 C2675179
UMLS 71 C2675179

Summaries for Cerebral Creatine Deficiency Syndrome 3

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. Children with arginine:glycine amidinotransferase deficiency may not gain weight and grow at the expected rate (failure to thrive), and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily.

MalaCards based summary : Cerebral Creatine Deficiency Syndrome 3, also known as arginine:glycine amidinotransferase deficiency, is related to cerebral creatine deficiency syndrome and creatine deficiency syndromes. An important gene associated with Cerebral Creatine Deficiency Syndrome 3 is GATM (Glycine Amidinotransferase), and among its related pathways/superpathways are Metabolism and Viral mRNA Translation. Affiliated tissues include brain and retina, 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.

OMIM : 56 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)

UniProtKB/Swiss-Prot : 73 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 : 74 Arginine:glycine amidinotransferase deficiency is an autosomal recessive cerebral creatine deficiency... 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:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 gowers sign 31 occasional (7.5%) HP:0003391
2 intellectual disability 31 HP:0001249
3 failure to thrive 31 HP:0001508
4 global developmental delay 31 HP:0001263
5 delayed speech and language development 31 HP:0000750
6 autism 31 HP:0000717
7 organic aciduria 31 HP:0001992
8 reduced brain creatine level by mrs 31 HP:0025051

Symptoms via clinical synopsis from OMIM:

56
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:

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:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.63 ASL GAMT GATM HAPLN1 OAT SLC6A8
2 homeostasis/metabolism MP:0005376 9.5 AGXT2 ASL GAMT GATM HAPLN1 OAT
3 renal/urinary system MP:0005367 9.1 AGXT2 ASL GAMT GATM OAT SLC6A8

Drugs & Therapeutics for Cerebral Creatine Deficiency Syndrome 3

Search Clinical Trials , 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:

40
Brain, Retina

Publications for Cerebral Creatine Deficiency Syndrome 3

Articles related to Cerebral Creatine Deficiency Syndrome 3:

(show all 18)
# Title Authors PMID Year
1
Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency. 61 56 6
22386973 2012
2
Arginine:glycine amidinotransferase deficiency: a treatable metabolic encephalomyopathy. 61 56 6
20625172 2010
3
Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. 61 56 6
11555793 2001
4
Creatine deficiency syndrome. A treatable myopathy due to arginine-glycine amidinotransferase (AGAT) deficiency. 56 6
23770102 2013
5
Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes. 56 6
23660394 2013
6
l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation. 56 6
20682460 2010
7
Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree. 56 6
12468279 2002
8
Reversible brain creatine deficiency in two sisters with normal blood creatine level. 56 6
10762163 2000
9
Arginine:glycine amidinotransferase (AGAT) deficiency in a newborn: early treatment can prevent phenotypic expression of the disease. 61 56
16769397 2006
10
Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. 6
23519317 2013
11
Creatine Deficiency Syndromes 6
20301745 2009
12
Creatine deficiency syndromes. 56
12701824 2003
13
Fifteen-year follow-up of Italian families affected by arginine glycine amidinotransferase deficiency. 61
28148286 2017
14
L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome. 61
23026748 2013
15
Creatine metabolism in urea cycle defects. 61
22644604 2012
16
Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology. 61
18652076 2007
17
Diagnostic enzyme assay that uses stable-isotope-labeled substrates to detect L-arginine:glycine amidinotransferase deficiency. 61
12709373 2003
18
Inborn errors of creatine metabolism and epilepsy: clinical features, diagnosis, and treatment. 61
12597058 2002

Variations for Cerebral Creatine Deficiency Syndrome 3

ClinVar genetic disease variations for Cerebral Creatine Deficiency Syndrome 3:

6 (show top 50) (show all 60) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GATM NM_001482.3(GATM):c.446G>A (p.Trp149Ter)SNV Pathogenic 7302 rs80338737 15:45661562-45661562 15:45369364-45369364
2 GATM NM_001482.3(GATM):c.484+1G>TSNV Pathogenic 21299 rs80338738 15:45661523-45661523 15:45369325-45369325
3 GATM NM_001482.3(GATM):c.1111dup (p.Met371fs)duplication Pathogenic 55918 rs397515542 15:45656145-45656146 15:45363947-45363948
4 GATM NM_001482.3(GATM):c.505C>T (p.Arg169Ter)SNV Pathogenic 55919 rs397514708 15:45660438-45660438 15:45368240-45368240
5 GATM NM_001482.3(GATM):c.608A>C (p.Tyr203Ser)SNV Pathogenic 55921 rs397514709 15:45660335-45660335 15:45368137-45368137
6 GATM NM_001482.3(GATM):c.216G>A (p.Trp72Ter)SNV Pathogenic 572733 rs1566842679 15:45668871-45668871 15:45376673-45376673
7 GATM NM_001482.3(GATM):c.1159+14A>GSNV Conflicting interpretations of pathogenicity 316210 rs368974196 15:45656084-45656084 15:45363886-45363886
8 GATM NM_001482.3(GATM):c.692C>G (p.Ser231Cys)SNV Conflicting interpretations of pathogenicity 205616 rs202225656 15:45658690-45658690 15:45366492-45366492
9 GATM NM_001482.3(GATM):c.1030A>G (p.Ile344Val)SNV Conflicting interpretations of pathogenicity 205608 rs747608698 15:45657007-45657007 15:45364809-45364809
10 GATM NM_001482.3(GATM):c.1041C>T (p.Asp347=)SNV Conflicting interpretations of pathogenicity 137450 rs139599307 15:45656996-45656996 15:45364798-45364798
11 GATM NM_001482.3(GATM):c.69+13C>TSNV Conflicting interpretations of pathogenicity 137454 rs573273215 15:45670570-45670570 15:45378372-45378372
12 GATM NM_001482.3(GATM):c.1159G>C (p.Gly387Arg)SNV Uncertain significance 316211 rs886051202 15:45656098-45656098 15:45363900-45363900
13 GATM NM_001482.3(GATM):c.701A>G (p.Asp234Gly)SNV Uncertain significance 205624 rs146057680 15:45658681-45658681 15:45366483-45366483
14 GATM NM_001482.3(GATM):c.7C>G (p.Arg3Gly)SNV Uncertain significance 205621 rs796052538 15:45670645-45670645 15:45378447-45378447
15 GATM NM_001482.3(GATM):c.1244G>A (p.Arg415Gln)SNV Uncertain significance 225921 rs374592247 15:45654335-45654335 15:45362137-45362137
16 GATM NM_001482.3(GATM):c.845G>A (p.Arg282His)SNV Uncertain significance 225918 rs371447931 15:45658377-45658377 15:45366179-45366179
17 GATM NM_001482.3(GATM):c.565C>T (p.Arg189Cys)SNV Uncertain significance 225915 rs377578020 15:45660378-45660378 15:45368180-45368180
18 GATM NM_001482.3(GATM):c.*699A>CSNV Uncertain significance 316205 rs750817737 15:45653608-45653608 15:45361410-45361410
19 GATM NM_001482.3(GATM):c.*104A>GSNV Uncertain significance 316208 rs886051201 15:45654203-45654203 15:45362005-45362005
20 GATM NM_001482.3(GATM):c.*27C>GSNV Uncertain significance 316209 rs200143728 15:45654280-45654280 15:45362082-45362082
21 GATM NM_001482.3(GATM):c.222C>T (p.Pro74=)SNV Uncertain significance 316212 rs774485349 15:45668865-45668865 15:45376667-45376667
22 GATM NM_001482.3(GATM):c.*847G>ASNV Uncertain significance 316202 rs1145087 15:45653460-45653460 15:45361262-45361262
23 GATM NM_001482.3(GATM):c.-72C>TSNV Uncertain significance 316213 rs886051203 15:45670723-45670723 15:45378525-45378525
24 GATM NM_001321015.2(GATM):c.-319+1757C>TSNV Uncertain significance 316216 rs745765661 15:45670925-45670925 15:45378727-45378727
25 GATM NM_001482.3(GATM):c.387A>T (p.Glu129Asp)SNV Uncertain significance 469138 rs756420233 15:45661621-45661621 15:45369423-45369423
26 GATM NM_001482.3(GATM):c.654G>A (p.Met218Ile)SNV Uncertain significance 469141 rs1555384217 15:45660289-45660289 15:45368091-45368091
27 GATM NM_001482.3(GATM):c.511A>T (p.Ile171Phe)SNV Uncertain significance 469139 rs747203599 15:45660432-45660432 15:45368234-45368234
28 GATM NM_001482.3(GATM):c.1106G>A (p.Arg369His)SNV Uncertain significance 498635 rs747557239 15:45656151-45656151 15:45363953-45363953
29 GATM NM_001482.3(GATM):c.581G>A (p.Arg194Gln)SNV Uncertain significance 536983 rs774017569 15:45660362-45660362 15:45368164-45368164
30 GATM NM_001482.3(GATM):c.710A>G (p.Lys237Arg)SNV Uncertain significance 536984 rs764877849 15:45658672-45658672 15:45366474-45366474
31 GATM NM_001321015.2(GATM):c.-318-1805T>CSNV Uncertain significance 316214 rs886051204 15:45670822-45670822 15:45378624-45378624
32 GATM NM_001482.3(GATM):c.844C>T (p.Arg282Cys)SNV Uncertain significance 198134 rs766583032 15:45658378-45658378 15:45366180-45366180
33 GATM NM_001482.3(GATM):c.685A>G (p.Ile229Val)SNV Uncertain significance 548592 rs570670146 15:45658697-45658697 15:45366499-45366499
34 GATM NM_001482.3(GATM):c.991A>C (p.Lys331Gln)SNV Uncertain significance 566779 rs1566839535 15:45657046-45657046 15:45364848-45364848
35 GATM NM_001482.3(GATM):c.625A>G (p.Lys209Glu)SNV Uncertain significance 567693 rs1393968087 15:45660318-45660318 15:45368120-45368120
36 covers 13 genes, none of which curated to show dosage sensitivity NC_000015.9:g.(?_45152372)_(45670671_?)dupduplication Uncertain significance 584325 15:45152372-45670671 15:44860174-45378473
37 GATM NM_001482.3(GATM):c.724G>A (p.Gly242Arg)SNV Uncertain significance 575063 rs1236954285 15:45658658-45658658 15:45366460-45366460
38 GATM NM_001482.3(GATM):c.37G>A (p.Gly13Ser)SNV Uncertain significance 578428 rs1566843333 15:45670615-45670615 15:45378417-45378417
39 GATM NM_001482.3(GATM):c.1209del (p.Gly404fs)deletion Uncertain significance 570204 rs1566838819 15:45654370-45654370 15:45362172-45362172
40 GATM NM_001482.3(GATM):c.1043-3T>CSNV Uncertain significance 587965 rs772985563 15:45656217-45656217 15:45364019-45364019
41 GATM NM_001482.3(GATM):c.1231G>A (p.Asp411Asn)SNV Uncertain significance 625953 rs768171759 15:45654348-45654348 15:45362150-45362150
42 GATM NM_001482.3(GATM):c.1162A>G (p.Ile388Val)SNV Uncertain significance 654184 15:45654417-45654417 15:45362219-45362219
43 GATM NM_001482.3(GATM):c.1085T>C (p.Val362Ala)SNV Uncertain significance 651345 15:45656172-45656172 15:45363974-45363974
44 GATM NM_001482.3(GATM):c.603A>C (p.Lys201Asn)SNV Uncertain significance 651610 15:45660340-45660340 15:45368142-45368142
45 GATM NM_001482.3(GATM):c.591G>T (p.Arg197Ser)SNV Uncertain significance 646168 15:45660352-45660352 15:45368154-45368154
46 GATM NM_001482.3(GATM):c.395A>G (p.Asn132Ser)SNV Uncertain significance 648568 15:45661613-45661613 15:45369415-45369415
47 GATM NM_001482.3(GATM):c.245G>A (p.Arg82Lys)SNV Uncertain significance 663209 15:45668842-45668842 15:45376644-45376644
48 GATM NM_001482.3(GATM):c.484+3A>GSNV Uncertain significance 665825 15:45661521-45661521 15:45369323-45369323
49 GATM NM_001482.3(GATM):c.42C>G (p.Ala14=)SNV Likely benign 536985 rs892312757 15:45670610-45670610 15:45378412-45378412
50 GATM NM_001482.3(GATM):c.114C>T (p.Ser38=)SNV Likely benign 469136 rs1555384721 15:45668973-45668973 15:45376775-45376775

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

73 (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

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
13.5 SLC6A8 OAT GATM GAMT ASL AGXT2
2
Show member pathways
13.13 SLC6A8 OAT GATM GAMT ASL AGXT2
3
Show member pathways
11.09 OAT GATM GAMT
4 10.88 ASL AGXT2
5
Show member pathways
10.85 GATM GAMT AGXT2
6
Show member pathways
10.3 OAT GATM GAMT ASL

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 9.26 SLC6A8 GAMT
2 cellular amino acid biosynthetic process GO:0008652 9.16 OAT ASL
3 creatine biosynthetic process GO:0006601 8.96 GATM GAMT
4 creatine metabolic process GO:0006600 8.8 SLC6A8 GATM GAMT

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

# Name GO ID Score Top Affiliating Genes
1 pyridoxal phosphate binding GO:0030170 8.96 OAT AGXT2
2 transaminase activity GO:0008483 8.62 OAT AGXT2

Sources for Cerebral Creatine Deficiency Syndrome 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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