X-linked creatine transporter deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: CRTR-D
MENTAL RETARDATION, X-LINKED, WITH SEIZURES, SHORT STATURE, AND MIDFACE HYPOPLASIA
CREATINE TRANSPORTER DEFECT
MENTAL RETARDATION, X-LINKED, WITH CREATINE TRANSPORT DEFICIENCY
CREATINE DEFICIENCY SYNDROME, X-LINKED
CCDS1
X-linked intellectual deficit - seizures - short stature - midface hypoplasia
Number of Symptoms 74
OrphanetNr: 52503
OMIM Id: 300352
ICD-10: E72.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: > 101 cases [Orphanet]
Inheritance: X-linked recessive
Not applicable
[Orphanet]
Age of onset: Infancy
Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of creatine biosynthesis
 -Rare genetic disease
 -Rare neurologic disease
Multiple congenital anomalies/dysmorphic syndrome-intellectual deficit
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease
Syndromic neurometabolic disease with X-linked intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0000275) Narrow face 76 / 7739
2
(HPO:0000252) Microcephaly Occasional [Orphanet] 832 / 7739
3
(HPO:0000272) Malar flattening Frequent [Orphanet] 277 / 7739
4
(HPO:0002058) Myopathic facies 26 / 7739
5
(HPO:0000303) Mandibular prognathia 179 / 7739
6
(HPO:0000194) Open mouth Frequent [Orphanet] 70 / 7739
7
(HPO:0011800) Midface retrusion 221 / 7739
8
(HPO:0000276) Long face 109 / 7739
9
(HPO:0000337) Broad forehead 116 / 7739
10
(HPO:0000298) Mask-like facies Occasional [Orphanet] 44 / 7739
11
(HPO:0000540) Hypermetropia 99 / 7739
12
(HPO:0000577) Exotropia 43 / 7739
13
(HPO:0000508) Ptosis Occasional [Orphanet] 459 / 7739
14
(HPO:0008583) Underfolded superior helices 1 / 7739
15
(HPO:0001276) Hypertonia Frequent [Orphanet] 317 / 7739
16
(HPO:0001250) Seizures Frequent [Orphanet] 1245 / 7739
17
(HPO:0007018) Attention deficit hyperactivity disorder 56 / 7739
18
(HPO:0002167) Neurological speech impairment Very frequent [Orphanet] 308 / 7739
19
(HPO:0000718) Aggressive behavior 109 / 7739
20
(HPO:0001288) Gait disturbance 318 / 7739
21
(HPO:0007057) Poor hand-eye coordination 1 / 7739
22
(HPO:0001270) Motor delay 322 / 7739
23
(HPO:0000717) Autism Frequent [Orphanet] 108 / 7739
24
(HPO:0000750) Delayed speech and language development 197 / 7739
25
(HPO:0100022) Abnormality of movement Frequent [Orphanet] 129 / 7739
26
(HPO:0001257) Spasticity 251 / 7739
27
(HPO:0000733) Stereotypy 58 / 7739
28
(HPO:0000735) Impaired social interactions 20 / 7739
29
(HPO:0001263) Global developmental delay 853 / 7739
30
(HPO:0001249) Intellectual disability 1089 / 7739
31
(HPO:0001332) Dystonia Frequent [Orphanet] 197 / 7739
32
(HPO:0002066) Gait ataxia Frequent [Orphanet] 327 / 7739
33
(HPO:0100851) Abnormal emotion/affect behavior Frequent [Orphanet] 85 / 7739
34
(HPO:0002251) Aganglionic megacolon Frequent [Orphanet] 78 / 7739
35
(HPO:0001838) Rocker bottom foot 85 / 7739
36
(HPO:0001822) Hallux valgus 70 / 7739
37
(HPO:0001761) Pes cavus 225 / 7739
38
(HPO:0001763) Pes planus 176 / 7739
39
(HPO:0001382) Joint hypermobility Occasional [Orphanet] 231 / 7739
40
(HPO:0001765) Hammertoe 63 / 7739
41
(HPO:0002019) Constipation Frequent [Orphanet] 194 / 7739
42
(HPO:0011968) Feeding difficulties 240 / 7739
43
(HPO:0002013) Vomiting 191 / 7739
44
(HPO:0002595) Ileus 4 / 7739
45
(HPO:0008872) Feeding difficulties in infancy 153 / 7739
46
(HPO:0005214) Intestinal obstruction Frequent [Orphanet] 35 / 7739
47
(HPO:0004326) Cachexia Frequent [Orphanet] 71 / 7739
48
(HPO:0004325) Decreased body weight 492 / 7739
49
(HPO:0004322) Short stature Frequent [Orphanet] 1232 / 7739
50
(HPO:0001508) Failure to thrive 454 / 7739
51
(HPO:0000098) Tall stature 74 / 7739
52
(HPO:0001582) Redundant skin Occasional [Orphanet] 51 / 7739
53
(HPO:0001939) Abnormality of metabolism/homeostasis Very frequent [Orphanet] 328 / 7739
54
(HPO:0001324) Muscle weakness 859 / 7739
55
(HPO:0010547) Muscle flaccidity 466 / 7739
56
(HPO:0001319) Neonatal hypotonia 101 / 7739
57
(HPO:0008947) Infantile muscular hypotonia 482 / 7739
58
(HPO:0001252) Muscular hypotonia Frequent [Orphanet] 990 / 7739
59
(OMIM) Stub thumb 2 / 7739
60
(OMIM) Increased plasma creatine 1 / 7739
61
(OMIM) Increased urinary creatine 1 / 7739
62
(HPO:0003593) Infantile onset 249 / 7739
63
(OMIM) Unfolded superior helices 1 / 7739
64
(OMIM) Long, thin face 3 / 7739
65
(OMIM) Impaired creatine uptake in fibroblasts 1 / 7739
66
(OMIM) Behavioral changes consistent with an autistic disorder 1 / 7739
67
(HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
68
(OMIM) Increased urinary creatine-to-creatinine ratio 1 / 7739
69
(OMIM) Decreased creatine signal seen on magnetic resonance spectroscopy 1 / 7739
70
(HPO:0002079) Hypoplasia of the corpus callosum 161 / 7739
71
(OMIM) Mild structural abnormalities seen MRI (in some patients) 1 / 7739
72
(HPO:0001419) X-linked recessive inheritance 189 / 7739
73
(OMIM) Speech and language delay, severe 1 / 7739
74
(HPO:0012448) Delayed myelination 51 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Diagnosis OMIM The biochemical test for CCDS1 is the urine creatine:creatinine ratio, which should be above 1.5 for a diagnosis of the disorder in males. Among 69 patients referred for SLC6A8 mutation testing, Comeaux et al. (2013) found that 45 ...
Clinical Description OMIM Salomons et al. (2001) reported a male patient with developmental delay and hypotonia. Proton magnetic resonance spectroscopic imaging (H-MRSI) of his brain revealed absence of the creatine signal. However, creatine in urine and plasma was increased, and guanidinoacetate ...
Molecular genetics OMIM In a male patient with developmental delay and defective creatine uptake, Salomons et al. (2001) identified a hemizygous nonsense mutation in the SLC6A8 gene (300036.0001). Three mildly affected female relatives were heterozygous for the mutation.

In ...

Diagnosis GeneReviews The cerebral creatine deficiency syndromes (CCDS) are inborn errors of creatine metabolism that include [Stöckler-Ipsiroglu & Salomons 2006]: ...
Clinical Description GeneReviews Intellectual disability and seizures are common to all three creatine deficiency syndromes. Intellectual disability is associated with expressive speech delay and behavioral disorder [Stöckler-Ipsiroglu & Salomons 2006]. ...
Genotype-Phenotype Correlations GeneReviews No genotype-phenotype correlations are known for any of the CCDS. ...
Differential Diagnosis GeneReviews Secondary (cerebral) creatine deficiencies have been observed in argininosuccinic aciduria (caused by argininosuccinate lyase deficiency), citrullinemia type 1 (caused by argininosuccinate synthetase enzyme deficiency) [van Spronsen et al 2006], and gyrate atrophy of the choroid and retina (caused by ornithine aminotransferase enzyme deficiency) [Nanto-Salonen et al 1999]. ...
Management GeneReviews To assess the extent of disease and needs of an individual diagnosed with CCDS the following investigations should be performed:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....