MCID: CRB151
MIFTS: 51

Cerebral Creatine Deficiency Syndrome 1

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

Aliases & Classifications for Cerebral Creatine Deficiency Syndrome 1

MalaCards integrated aliases for Cerebral Creatine Deficiency Syndrome 1:

Name: Cerebral Creatine Deficiency Syndrome 1 53 12 71
Creatine Transporter Deficiency 12 24 55 14
X-Linked Creatine Deficiency Syndrome 49 24 71
Creatine Deficiency, X-Linked 49 28 69
Creatine Transporter Defect 53 24 71
Slc6a8 Deficiency 12 24 55
X-Linked Creatine Transporter Deficiency 49 55
Creatine Deficiency Syndrome, X-Linked 53 13
X-Linked Creatine Deficiency 49 24
Ccds1 53 71
Mental Retardation, X-Linked, with Seizures, Short Stature, and Midface Hypoplasia 53
Mental Retardation , X-Linked with Seizures, Short Stature and Midface Hypoplasia 49
X-Linked Mental Retardation with Seizures, Short Stature, and Midface Hypoplasia 71
Mental Retardation , X-Linked, with Creatine Transport Deficiency 49
Mental Retardation, X-Linked, with Creatine Transport Deficiency 53
X-Linked Mental Retardation with Creatine Transport Deficiency 71
Slc6a8-Related Creatine Transporter Deficiency 24

Characteristics:

Orphanet epidemiological data:

55
x-linked creatine transporter deficiency
Inheritance: Not applicable,X-linked recessive; Age of onset: Childhood,Infancy; Age of death: adult;

OMIM:

53
Inheritance:
x-linked recessive

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


HPO:

31
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 : 49 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 cerebral creatine deficiency syndrome 3 and cerebral creatine deficiency syndrome 2, and has symptoms including ataxia, constipation and cachexia. 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 Increased shRNA abundance (Z-score > 2)

Genetics Home Reference : 24 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 : 53 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)

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.

Related Diseases for Cerebral Creatine Deficiency Syndrome 1

Diseases related to Cerebral Creatine Deficiency Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 cerebral creatine deficiency syndrome 3 30.5 GAMT GATM SLC6A8
2 cerebral creatine deficiency syndrome 2 30.4 GAMT GATM SLC6A8
3 creatine deficiency syndromes 29.0 GAMT GATM SLC6A8
4 cerebritis 10.0
5 autism 9.9
6 aging 9.8
7 global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies 9.8
8 autism spectrum disorder 9.8
9 epilepsy 9.8
10 mitochondrial disorders 9.8
11 encephalopathy 9.8
12 amino acid metabolic disorder 9.6 GAMT SLC6A8
13 cerebral creatine deficiency syndrome 8.5 BCAP31 FABP3 GAMT GATM SLC6A8

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:

53
Abdomen Gastroin testinal:
constipation
vomiting
ileus
poor feeding
megacolon

Head And Neck Eyes:
ptosis
exotropia
hypermetropia

Head And Neck Head:
microcephaly
decreased head circumference

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

Growth Weight:
low weight

Head And Neck Ears:
unfolded superior helices

Skeletal Feet:
pes cavus (less common)

Neurologic Central Nervous System:
seizures
dystonia
spasticity
motor delay
delayed myelination
more
Growth Other:
failure to thrive

Growth Height:
short stature
tall stature

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

Skeletal Limbs:
hyperextensible joints

Skeletal Hands:
stub thumb

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


Clinical features from OMIM:

300352

Human phenotypes related to Cerebral Creatine Deficiency Syndrome 1:

55 31 (show top 50) (show all 54)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 frequent (33%) Frequent (79-30%) HP:0001251
2 constipation 55 31 frequent (33%) Frequent (79-30%) HP:0002019
3 cachexia 55 31 frequent (33%) Frequent (79-30%) HP:0004326
4 seizures 55 31 hallmark (90%) Very frequent (99-80%) HP:0001250
5 athetosis 55 31 frequent (33%) Frequent (79-30%) HP:0002305
6 dystonia 55 31 frequent (33%) Frequent (79-30%) HP:0001332
7 malar flattening 55 31 frequent (33%) Frequent (79-30%) HP:0000272
8 ptosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000508
9 intellectual disability 55 31 hallmark (90%) Very frequent (99-80%) HP:0001249
10 muscular hypotonia 55 31 frequent (33%) Frequent (79-30%) HP:0001252
11 chorea 55 31 frequent (33%) Frequent (79-30%) HP:0002072
12 global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0001263
13 delayed speech and language development 55 31 hallmark (90%) Very frequent (99-80%) HP:0000750
14 microcephaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0000252
15 short stature 55 31 frequent (33%) Frequent (79-30%) HP:0004322
16 hypertonia 55 31 frequent (33%) Frequent (79-30%) HP:0001276
17 joint hyperflexibility 55 31 occasional (7.5%) Occasional (29-5%) HP:0005692
18 mask-like facies 55 31 occasional (7.5%) Occasional (29-5%) HP:0000298
19 aganglionic megacolon 55 31 frequent (33%) Frequent (79-30%) HP:0002251
20 ileus 55 31 frequent (33%) Frequent (79-30%) HP:0002595
21 open mouth 55 31 frequent (33%) Frequent (79-30%) HP:0000194
22 redundant skin 55 31 occasional (7.5%) Occasional (29-5%) HP:0001582
23 autistic behavior 55 31 frequent (33%) Frequent (79-30%) HP:0000729
24 hyperactivity 55 31 frequent (33%) Frequent (79-30%) HP:0000752
25 self-mutilation 55 31 frequent (33%) Frequent (79-30%) HP:0000742
26 abnormality of creatine metabolism 55 31 hallmark (90%) Very frequent (99-80%) HP:0012113
27 vomiting 31 HP:0002013
28 spasticity 31 HP:0001257
29 gait disturbance 31 HP:0001288
30 failure to thrive 31 HP:0001508
31 mandibular prognathia 31 HP:0000303
32 neonatal hypotonia 31 HP:0001319
33 feeding difficulties in infancy 31 HP:0008872
34 stereotypy 31 HP:0000733
35 abnormality of metabolism/homeostasis 31 HP:0001939
36 attention deficit hyperactivity disorder 31 HP:0007018
37 pes cavus 31 HP:0001761
38 broad forehead 31 HP:0000337
39 impaired social interactions 31 HP:0000735
40 narrow face 31 HP:0000275
41 joint hypermobility 31 HP:0001382
42 long face 31 HP:0000276
43 aggressive behavior 31 HP:0000718
44 midface retrusion 31 HP:0011800
45 tall stature 31 HP:0000098
46 motor delay 31 HP:0001270
47 myopathic facies 31 HP:0002058
48 hypoplasia of the corpus callosum 31 HP:0002079
49 generalized hypotonia 31 HP:0001290
50 exotropia 31 HP:0000577

UMLS symptoms related to Cerebral Creatine Deficiency Syndrome 1:


vomiting, seizures, muscle spasticity, constipation

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

25 (show all 24)
# 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 GATM GAMT
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:

43
# 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):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cisplatin Approved Phase 2 15663-27-1 2767 441203 84093
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 Approved, Investigational, Nutraceutical 57-00-1 586

Interventional clinical trials:


# 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:

# Genetic test Affiliating Genes
1 Creatine Deficiency, X-Linked 28 SLC6A8

Anatomical Context for Cerebral Creatine Deficiency Syndrome 1

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

38
Brain, Heart, Skin, Eye

Publications for Cerebral Creatine Deficiency Syndrome 1

Articles related to Cerebral Creatine Deficiency Syndrome 1:

(show all 30)
# Title Authors Year
1
A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging. ( 27466184 )
2016
2
Creatine Transporter Deficiency: Screening of Males with Neurodevelopmental Disorders and Neurocognitive Characterization of a Case. ( 27096572 )
2016
3
Variable White Matter Atrophy and Intellectual Development in a Family With X-linked Creatine Transporter Deficiency Despite Genotypic Homogeneity. ( 28065824 )
2016
4
Creatine transporter deficiency: Novel mutations and functional studies. ( 27408820 )
2016
5
Creatine transporter deficiency leads to increased whole body and cellular metabolism. ( 27401086 )
2016
6
Estimated carrier frequency of creatine transporter deficiency in females in the general population using functional characterization of novel missense variants in the SLC6A8 gene. ( 25861866 )
2015
7
A novel SLC6A8 mutation associated with motor dysfunction in a child exhibiting creatine transporter deficiency. ( 27081545 )
2015
8
Effects of amide creatine derivatives in brain hippocampal slices, and their possible usefulness for curing creatine transporter deficiency. ( 24213972 )
2014
9
Dodecyl creatine ester and lipid nanocapsule: a double strategy for the treatment of creatine transporter deficiency. ( 24559037 )
2014
10
X-linked creatine transporter deficiency: clinical aspects and pathophysiology. ( 24789340 )
2014
11
A novel mouse model of creatine transporter deficiency. ( 25485098 )
2014
12
Female mice heterozygous for creatine transporter deficiency show moderate cognitive deficits. ( 23716276 )
2014
13
Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. ( 23644449 )
2013
14
Synthesis and biological evaluation of new creatine fatty esters revealed dodecyl creatine ester as a promising drug candidate for the treatment of the creatine transporter deficiency. ( 23697594 )
2013
15
Urine screening for patients with developmental disabilities detected a patient with creatine transporter deficiency due to a novel missense mutation in SLC6A8. ( 24045174 )
2013
16
New insights into creatine transporter deficiency: the importance of recycling creatine in the brain. ( 22968583 )
2013
17
Cyclocreatine treatment improves cognition in mice with creatine transporter deficiency. ( 22751104 )
2012
18
Glycine and L-arginine treatment causes hyperhomocysteinemia in cerebral creatine transporter deficiency patients. ( 23430891 )
2012
19
Searching for a therapy of creatine transporter deficiency: some effects of creatine ethyl ester in brain slices in vitro. ( 21963865 )
2011
20
Response to creatine analogs in fibroblasts and patients with creatine transporter deficiency. ( 19955008 )
2010
21
Creatine transporter deficiency in two half-brothers. ( 20602486 )
2010
22
A new case of creatine transporter deficiency associated with mild clinical phenotype and a novel mutation in the SLC6A8 gene. ( 20002129 )
2010
23
X-linked creatine transporter deficiency presenting as a mitochondrial disorder. ( 20501887 )
2010
24
Creatine transporter deficiency in two adult patients with static encephalopathy. ( 19319661 )
2009
25
Epilepsy spectrum in cerebral creatine transporter deficiency. ( 19706062 )
2009
26
Screening of male patients with autism spectrum disorder for creatine transporter deficiency. ( 18461508 )
2007
27
Creatine transporter deficiency: prevalence among patients with mental retardation and pitfalls in metabolite screening. ( 17825809 )
2007
28
[Cerebral creatine transporter deficiency: an infradiagnosed neurometabolic disease]. ( 17385170 )
2007
29
X-Linked creatine transporter deficiency in two patients with severe mental retardation and autism. ( 16601898 )
2006
30
X-linked creatine transporter deficiency: clinical description of a patient with a novel SLC6A8 gene mutation. ( 16086185 )
2005

Variations for Cerebral Creatine Deficiency Syndrome 1

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

71 (show all 12)
# 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)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC6A8 SLC6A8, 3-BP DEL, 1006AAC deletion Pathogenic
2 SLC6A8 NM_005629.3(SLC6A8): c.1540C> T (p.Arg514Ter) single nucleotide variant Pathogenic rs122453113 GRCh37 Chromosome X, 152960032: 152960032
3 SLC6A8 NM_005629.3(SLC6A8): c.1141G> C (p.Gly381Arg) single nucleotide variant Pathogenic rs122453114 GRCh37 Chromosome X, 152959041: 152959041
4 SLC6A8 NM_005629.3(SLC6A8): c.1222_1224delTTC (p.Phe408del) deletion Pathogenic rs80338740 GRCh37 Chromosome X, 152959440: 152959442
5 SLC6A8 SLC6A8, 1-BP INS, 950A insertion Pathogenic
6 SLC6A8 NM_005629.3(SLC6A8): c.259G> A (p.Gly87Arg) single nucleotide variant Pathogenic rs122453115 GRCh37 Chromosome X, 152954288: 152954288
7 SLC6A8 SLC6A8, IVS1AS, A-G, -2 single nucleotide variant Pathogenic
8 SLC6A8 NM_005629.3(SLC6A8): c.1011C> G (p.Cys337Trp) single nucleotide variant Pathogenic rs122453116 GRCh37 Chromosome X, 152958816: 152958816
9 SLC6A8 NM_005629.3(SLC6A8): c.395G> T (p.Gly132Val) single nucleotide variant Pathogenic rs122453117 GRCh37 Chromosome X, 152956759: 152956759
10 SLC6A8 NM_005629.3(SLC6A8): c.1473C> G (p.Cys491Trp) single nucleotide variant Pathogenic rs122453118 GRCh37 Chromosome X, 152959879: 152959879
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:

# 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:

# 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
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
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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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