MCID: CRB151
MIFTS: 46

Cerebral Creatine Deficiency Syndrome 1

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

Aliases & Classifications for Cerebral Creatine Deficiency Syndrome 1

MalaCards integrated aliases for Cerebral Creatine Deficiency Syndrome 1:

Name: Cerebral Creatine Deficiency Syndrome 1 54 12 71
Creatine Transporter Deficiency 12 25 56 14
X-Linked Creatine Deficiency Syndrome 50 25 71
Creatine Deficiency, X-Linked 50 29 69
Slc6a8 Deficiency 12 25 56
X-Linked Creatine Transporter Deficiency 50 56
X-Linked Creatine Deficiency 50 25
Creatine Transporter Defect 25 71
Mental Retardation , X-Linked with Seizures, Short Stature and Midface Hypoplasia 50
X-Linked Mental Retardation with Seizures, Short Stature, and Midface Hypoplasia 71
Mental Retardation , X-Linked, with Creatine Transport Deficiency 50
X-Linked Mental Retardation with Creatine Transport Deficiency 71
Slc6a8-Related Creatine Transporter Deficiency 25
Creatine Deficiency Syndrome, X-Linked 13
Ccds1 71

Characteristics:

Orphanet epidemiological data:

56
x-linked creatine transporter deficiency
Inheritance: Not applicable,X-linked recessive; Age of onset: Childhood,Infancy; Age of death: adult;

OMIM:

54
Miscellaneous:
onset in first months of life
carrier females may show neuropsychologic impairment

Inheritance:
x-linked recessive


HPO:

32
cerebral creatine deficiency syndrome 1:
Onset and clinical course infantile onset
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Cerebral Creatine Deficiency Syndrome 1

NIH Rare Diseases : 50 x-linked creatine deficiency is a rare condition that primarily affects the brain. signs and symptoms generally develop before age 2 and may include mild to severe intellectual disability; delayed speech development, behavioral problems (i.e. autistic features, hyperactivity), and seizures. less commonly, affected people may have distinctive facial features, heart abnormalities, and gastrointestinal disorders. x-linked creatine deficiency is caused by changes (mutations) in the slc6a8 gene and is inherited in an x-linked manner. treatment with high doses of creatine monohydrate, l-arginine, and l-glycine has been used to treat some of the symptoms associated with x-linked creatine deficiency with variable success. last updated: 11/5/2015

MalaCards based summary : Cerebral Creatine Deficiency Syndrome 1, also known as creatine transporter deficiency, is related to slc6a8-related creatine transporter deficiency and cerebral creatine deficiency syndrome 3, and has symptoms including short stature, dystonia and chorea. An important gene associated with Cerebral Creatine Deficiency Syndrome 1 is SLC6A8 (Solute Carrier Family 6 Member 8), and among its related pathways/superpathways are Arginine and proline metabolism and Glycine, serine and threonine metabolism. The drugs Cisplatin and Fluorouracil have been mentioned in the context of this disorder. Affiliated tissues include brain, heart and skin, and related phenotypes are Increased shRNA abundance (Z-score > 2) and adipose tissue

UniProtKB/Swiss-Prot : 71 Cerebral creatine deficiency syndrome 1: An X-linked disorder of creatine transport characterized by mental retardation, severe speech delay, behavioral abnormalities, and seizures. Carrier females may show mild neuropsychologic impairment.

Genetics Home Reference : 25 X-linked creatine deficiency is an inherited disorder that primarily affects the brain. People with this disorder have intellectual disability, which can range from mild to severe, and delayed speech development. Some affected individuals develop behavioral disorders such as attention deficit hyperactivity disorder or autistic behaviors that affect communication and social interaction. They may also experience seizures. Children with X-linked creatine deficiency may experience slow growth and exhibit delayed development of motor skills such as sitting and walking. Affected individuals tend to tire easily.

OMIM : 54
Cerebral creatine deficiency syndrome-1 is an X-linked disorder of creatine (Cr) transport characterized by mental retardation, severe speech delay, behavioral abnormalities, and seizures. It has a prevalence of 0.3 to 3.5% in males. Carrier females may show mild neuropsychologic impairment (summary by van de Kamp et al., 2011). (300352)

Related Diseases for Cerebral Creatine Deficiency Syndrome 1

Graphical network of the top 20 diseases related to Cerebral Creatine Deficiency Syndrome 1:



Diseases related to Cerebral Creatine Deficiency Syndrome 1

Symptoms & Phenotypes for Cerebral Creatine Deficiency Syndrome 1

Symptoms via clinical synopsis from OMIM:

54

Growth- Height:
short stature
tall stature

Neurologic- Central Nervous System:
hypotonia
mental retardation
dystonia
thin corpus callosum
spasticity
more
Head And Neck- Head:
microcephaly
decreased head circumference

Head And Neck- Face:
midface hypoplasia
myopathic facies
broad forehead
prominent chin
long, thin face

Neurologic- Behavioral Psychiatric Manifestations:
aggressive behavior
attention deficit hyperactivity disorder
impaired social interaction
behavioral changes consistent with an autistic disorder
stereotypical motor behaviors

Laboratory- Abnormalities:
increased urinary creatine
impaired creatine uptake in fibroblasts
increased plasma creatine
increased urinary creatine-to-creatinine ratio

Head And Neck- Ears:
unfolded superior helices

Growth- Other:
failure to thrive

Head And Neck- Eyes:
ptosis
hypermetropia
exotropia

Abdomen- Gastroin testinal:
poor feeding
vomiting
constipation
megacolon
ileus

Growth- Weight:
low weight

Skeletal- Feet:
pes cavus (less common)

Skeletal- Limbs:
hyperextensible joints

Skeletal- Hands:
stub thumb


Clinical features from OMIM:

300352

Human phenotypes related to Cerebral Creatine Deficiency Syndrome 1:

56 32 (show top 50) (show all 53)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 frequent (33%) Frequent (79-30%) HP:0004322
2 dystonia 56 32 frequent (33%) Frequent (79-30%) HP:0001332
3 chorea 56 32 frequent (33%) Frequent (79-30%) HP:0002072
4 ataxia 56 32 frequent (33%) Frequent (79-30%) HP:0001251
5 seizures 56 32 hallmark (90%) Very frequent (99-80%) HP:0001250
6 hypertonia 56 32 frequent (33%) Frequent (79-30%) HP:0001276
7 ptosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0000508
8 microcephaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0000252
9 global developmental delay 56 32 hallmark (90%) Very frequent (99-80%) HP:0001263
10 intellectual disability 56 32 hallmark (90%) Very frequent (99-80%) HP:0001249
11 hyperactivity 56 32 frequent (33%) Frequent (79-30%) HP:0000752
12 self-mutilation 56 32 frequent (33%) Frequent (79-30%) HP:0000742
13 open mouth 56 32 frequent (33%) Frequent (79-30%) HP:0000194
14 constipation 56 32 frequent (33%) Frequent (79-30%) HP:0002019
15 joint hyperflexibility 56 32 occasional (7.5%) Occasional (29-5%) HP:0005692
16 muscular hypotonia 56 32 frequent (33%) Frequent (79-30%) HP:0001252
17 malar flattening 56 32 frequent (33%) Frequent (79-30%) HP:0000272
18 redundant skin 56 32 occasional (7.5%) Occasional (29-5%) HP:0001582
19 athetosis 56 32 frequent (33%) Frequent (79-30%) HP:0002305
20 autistic behavior 56 32 frequent (33%) Frequent (79-30%) HP:0000729
21 mask-like facies 56 32 occasional (7.5%) Occasional (29-5%) HP:0000298
22 cachexia 56 32 frequent (33%) Frequent (79-30%) HP:0004326
23 delayed speech and language development 56 32 hallmark (90%) Very frequent (99-80%) HP:0000750
24 aganglionic megacolon 56 32 frequent (33%) Frequent (79-30%) HP:0002251
25 ileus 56 32 frequent (33%) Frequent (79-30%) HP:0002595
26 abnormality of creatine metabolism 56 32 hallmark (90%) Very frequent (99-80%) HP:0012113
27 failure to thrive 32 HP:0001508
28 spasticity 32 HP:0001257
29 long face 32 HP:0000276
30 myopathic facies 32 HP:0002058
31 vomiting 32 HP:0002013
32 neonatal hypotonia 32 HP:0001319
33 broad forehead 32 HP:0000337
34 hypoplasia of the corpus callosum 32 HP:0002079
35 pes cavus 32 HP:0001761
36 aggressive behavior 32 HP:0000718
37 joint hypermobility 32 HP:0001382
38 motor delay 32 HP:0001270
39 delayed myelination 32 HP:0012448
40 midface retrusion 32 HP:0011800
41 narrow face 32 HP:0000275
42 hypermetropia 32 HP:0000540
43 tall stature 32 HP:0000098
44 feeding difficulties in infancy 32 HP:0008872
45 exotropia 32 HP:0000577
46 gait disturbance 32 HP:0001288
47 attention deficit hyperactivity disorder 32 HP:0007018
48 impaired social interactions 32 HP:0000735
49 poor hand-eye coordination 32 HP:0007057
50 mandibular prognathia 32 HP:0000303

UMLS symptoms related to Cerebral Creatine Deficiency Syndrome 1:


constipation, muscle spasticity, seizures, vomiting

GenomeRNAi Phenotypes related to Cerebral Creatine Deficiency Syndrome 1 according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-103 10.05 GATM
2 Increased shRNA abundance (Z-score > 2) GR00366-A-105 10.05 SLC6A8
3 Increased shRNA abundance (Z-score > 2) GR00366-A-11 10.05 SLC6A8
4 Increased shRNA abundance (Z-score > 2) GR00366-A-120 10.05 SLC6A8
5 Increased shRNA abundance (Z-score > 2) GR00366-A-124 10.05 GAMT GATM
6 Increased shRNA abundance (Z-score > 2) GR00366-A-125 10.05 GATM
7 Increased shRNA abundance (Z-score > 2) GR00366-A-126 10.05 GATM
8 Increased shRNA abundance (Z-score > 2) GR00366-A-132 10.05 SLC6A8
9 Increased shRNA abundance (Z-score > 2) GR00366-A-137 10.05 SLC6A8
10 Increased shRNA abundance (Z-score > 2) GR00366-A-143 10.05 GAMT
11 Increased shRNA abundance (Z-score > 2) GR00366-A-158 10.05 GATM
12 Increased shRNA abundance (Z-score > 2) GR00366-A-159 10.05 GATM
13 Increased shRNA abundance (Z-score > 2) GR00366-A-161 10.05 GAMT
14 Increased shRNA abundance (Z-score > 2) GR00366-A-214 10.05 GAMT
15 Increased shRNA abundance (Z-score > 2) GR00366-A-22 10.05 GATM
16 Increased shRNA abundance (Z-score > 2) GR00366-A-52 10.05 SLC6A8
17 Increased shRNA abundance (Z-score > 2) GR00366-A-63 10.05 GAMT
18 Increased shRNA abundance (Z-score > 2) GR00366-A-67 10.05 GAMT SLC6A8
19 Increased shRNA abundance (Z-score > 2) GR00366-A-73 10.05 GATM
20 Increased shRNA abundance (Z-score > 2) GR00366-A-74 10.05 SLC6A8
21 Increased shRNA abundance (Z-score > 2) GR00366-A-78 10.05 GATM
22 Increased shRNA abundance (Z-score > 2) GR00366-A-81 10.05 GAMT
23 Increased shRNA abundance (Z-score > 2) GR00366-A-88 10.05 GAMT
24 Increased shRNA abundance (Z-score > 2) GR00366-A-9 10.05 GAMT SLC6A8

MGI Mouse Phenotypes related to Cerebral Creatine Deficiency Syndrome 1:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 8.92 FABP3 GAMT GATM SLC6A8

Drugs & Therapeutics for Cerebral Creatine Deficiency Syndrome 1

Drugs for Cerebral Creatine Deficiency Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cisplatin Approved Phase 2 15663-27-1 84093 441203 2767
2
Fluorouracil Approved Phase 2 51-21-8 3385
3
Docetaxel Approved May 1996, Investigational Phase 2 114977-28-5 148124 9877265
4 Antimitotic Agents Phase 2
5
Creatine Nutraceutical 57-00-1 586

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Cyclin D1 Based TPF Induction Chemotherapy for Oral Squamous Cell Carcinoma Patients at Clinical N2 Stage Recruiting NCT02290145 Phase 2 TPF group
2 Observational Study of Males With Creatine Transporter Deficiency Recruiting NCT02931682
3 Biomarker for Creatine Deficiency Syndromes Recruiting NCT02934854

Search NIH Clinical Center for Cerebral Creatine Deficiency Syndrome 1

Genetic Tests for Cerebral Creatine Deficiency Syndrome 1

Genetic tests related to Cerebral Creatine Deficiency Syndrome 1:

id Genetic test Affiliating Genes
1 Creatine Deficiency, X-Linked 29

Anatomical Context for Cerebral Creatine Deficiency Syndrome 1

MalaCards organs/tissues related to Cerebral Creatine Deficiency Syndrome 1:

39
Brain, Heart, Skin, Eye

Publications for Cerebral Creatine Deficiency Syndrome 1

Variations for Cerebral Creatine Deficiency Syndrome 1

UniProtKB/Swiss-Prot genetic disease variations for Cerebral Creatine Deficiency Syndrome 1:

71 (show all 12)
id Symbol AA change Variation ID SNP ID
1 SLC6A8 p.Gly87Arg VAR_020525 rs122453115
2 SLC6A8 p.Gly381Arg VAR_020526 rs122453114
3 SLC6A8 p.Pro390Leu VAR_020527
4 SLC6A8 p.Pro554Leu VAR_020529 rs397515559
5 SLC6A8 p.Gly132Val VAR_063707 rs122453117
6 SLC6A8 p.Cys337Trp VAR_063708 rs122453116
7 SLC6A8 p.Cys491Trp VAR_063709 rs122453118
8 SLC6A8 p.Tyr80His VAR_071791
9 SLC6A8 p.Gly383Cys VAR_071792
10 SLC6A8 p.Ala448Asp VAR_071793
11 SLC6A8 p.Val539Ile VAR_071794 rs782354054
12 SLC6A8 p.Arg391Trp VAR_075566

ClinVar genetic disease variations for Cerebral Creatine Deficiency Syndrome 1:

6 (show all 15)
id Gene Variation Type Significance SNP ID Assembly Location
1 SLC6A8 NM_005629.3(SLC6A8): c.1540C> T (p.Arg514Ter) single nucleotide variant Pathogenic rs122453113 GRCh37 Chromosome X, 152960032: 152960032
2 SLC6A8 NM_005629.3(SLC6A8): c.1141G> C (p.Gly381Arg) single nucleotide variant Pathogenic rs122453114 GRCh37 Chromosome X, 152959041: 152959041
3 SLC6A8 NM_005629.3(SLC6A8): c.1222_1224delTTC (p.Phe408del) deletion Pathogenic rs80338740 GRCh37 Chromosome X, 152959440: 152959442
4 SLC6A8 SLC6A8, 1-BP INS, 950A insertion Pathogenic
5 SLC6A8 NM_005629.3(SLC6A8): c.259G> A (p.Gly87Arg) single nucleotide variant Pathogenic rs122453115 GRCh37 Chromosome X, 152954288: 152954288
6 SLC6A8 SLC6A8, IVS1AS, A-G, -2 single nucleotide variant Pathogenic
7 SLC6A8 NM_005629.3(SLC6A8): c.1011C> G (p.Cys337Trp) single nucleotide variant Pathogenic rs122453116 GRCh37 Chromosome X, 152958816: 152958816
8 SLC6A8 NM_005629.3(SLC6A8): c.395G> T (p.Gly132Val) single nucleotide variant Pathogenic rs122453117 GRCh37 Chromosome X, 152956759: 152956759
9 SLC6A8 NM_005629.3(SLC6A8): c.1473C> G (p.Cys491Trp) single nucleotide variant Pathogenic rs122453118 GRCh37 Chromosome X, 152959879: 152959879
10 SLC6A8 SLC6A8, 3-BP DEL, 1006AAC deletion Pathogenic
11 SLC6A8 NM_005629.3(SLC6A8): c.321_323delCTT (p.Phe107del) deletion Pathogenic rs80338739 GRCh37 Chromosome X, 152955888: 152955890
12 SLC6A8 NM_005629.3(SLC6A8): c.1631C> T (p.Pro544Leu) single nucleotide variant Pathogenic rs397515558 GRCh37 Chromosome X, 152960208: 152960208
13 SLC6A8 NM_005629.3(SLC6A8): c.1661C> T (p.Pro554Leu) single nucleotide variant Pathogenic rs397515559 GRCh37 Chromosome X, 152960238: 152960238
14 SLC6A8 NM_005629.3(SLC6A8): c.974_975delCA (p.Thr325Serfs) deletion Pathogenic rs1060502808 GRCh38 Chromosome X, 153693324: 153693325
15 SLC6A8 NM_005629.3(SLC6A8): c.1583delC (p.Pro528Argfs) deletion Pathogenic GRCh38 Chromosome X, 153694620: 153694620

Expression for Cerebral Creatine Deficiency Syndrome 1

Search GEO for disease gene expression data for Cerebral Creatine Deficiency Syndrome 1.

Pathways for Cerebral Creatine Deficiency Syndrome 1

Pathways related to Cerebral Creatine Deficiency Syndrome 1 according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
10.91 GAMT GATM
2
Show member pathways
10.67 GAMT GATM
3
Show member pathways
10 GAMT GATM

GO Terms for Cerebral Creatine Deficiency Syndrome 1

Biological processes related to Cerebral Creatine Deficiency Syndrome 1 according to GeneCards Suite gene sharing:

id 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 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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