Creatine transporter deficiency

Summary

Creatine transporter deficiency (MONDO:0010305) is a disease caused by SLC6A8 (GenCC Definitive), with 4 cohort genes and 6 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: SLC6A8 (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 1,069
• Phenotypes (HPO): 26
• Clinical trials: 6

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		150	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0012113	Abnormality of creatine metabolism	Very frequent (80-99%)
HP:0000194	Open mouth	Frequent (30-79%)
HP:0000272	Malar flattening	Frequent (30-79%)
HP:0000729	Autistic behavior	Frequent (30-79%)
HP:0000742	Self-mutilation	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001276	Hypertonia	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0002019	Constipation	Frequent (30-79%)
HP:0002072	Chorea	Frequent (30-79%)
HP:0000752	Hyperactivity	Frequent (30-79%)
HP:0002251	Aganglionic megacolon	Frequent (30-79%)
HP:0002305	Athetosis	Frequent (30-79%)
HP:0002595	Ileus	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0004326	Cachexia	Frequent (30-79%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000298	Mask-like facies	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0001582	Redundant skin	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	creatine transporter deficiency
Mondo ID	MONDO:0010305
MeSH	C535598
OMIM	300352
Orphanet	52503
DOID	DOID:0050800
NCIT	C125665
SNOMED CT	698290008
UMLS	C1845862
MedGen	337451
GARD	0001608
NORD	1966
Is cancer (heuristic)	no

Also known as: CCDS1 · cerebral creatine deficiency syndrome 1 · cerebral creatine deficiency syndrome 1, X-linked recessive · cerebral creatine deficiency syndrome type 1 · creatine deficiency, X-linked · creatine transporter deficiency · intellectual disability, X-linked with seizures, short stature and midface hypoplasia · intellectual disability, X-linked, with creatine transport deficiency · mental retardation, X-linked with seizures, short stature and midface hypoplasia · mental retardation, X-linked, with creatine Transport deficiency · mental retardation, X-linked, with creatine transport deficiency · mental retardation, X-linked, with seizures, short stature, and midface hypoplasia · SLC6A8 deficiency · X-linked creatine deficiency · X-linked creatine deficiency syndrome

Data availability: 1,069 ClinVar variants · 174 ClinGen variant curations · 5 GenCC gene-disease records · 32 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › cerebral creatine deficiency syndrome › creatine transporter deficiency

Related subtypes (2): AGAT deficiency, guanidinoacetate methyltransferase deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

336 likely benign, 124 uncertain significance, 53 pathogenic, 37 benign, 25 likely pathogenic, 14 benign/likely benign, 9 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2422157	NC_000023.10:g.(?152014869)(155171615_?)del	ABCD1	Pathogenic	criteria provided, single submitter
1064525	NM_005629.4(SLC6A8):c.1394_1399del (p.Gly465_Met467delinsVal)	SLC6A8	Pathogenic	no assertion criteria provided
1069434	NM_005629.4(SLC6A8):c.1108C>T (p.Gln370Ter)	SLC6A8	Pathogenic	criteria provided, multiple submitters, no conflicts
1070967	NM_005629.4(SLC6A8):c.1551del (p.Trp518fs)	SLC6A8	Pathogenic	criteria provided, single submitter
1076955	NM_005629.4(SLC6A8):c.1393-12_1395del	SLC6A8	Pathogenic	criteria provided, single submitter
11696	NM_005629.4(SLC6A8):c.1540C>T (p.Arg514Ter)	SLC6A8	Pathogenic	reviewed by expert panel
11697	NM_005629.4(SLC6A8):c.1141G>C (p.Gly381Arg)	SLC6A8	Pathogenic	reviewed by expert panel
11698	NM_005629.4(SLC6A8):c.1216TTC[2] (p.Phe408del)	SLC6A8	Pathogenic	reviewed by expert panel
11699	NM_005629.4(SLC6A8):c.950dup (p.Tyr317Ter)	SLC6A8	Pathogenic	reviewed by expert panel
11701	NM_005629.4(SLC6A8):c.263-2A>G	SLC6A8	Pathogenic	reviewed by expert panel
11702	NM_005629.4(SLC6A8):c.1011C>G (p.Cys337Trp)	SLC6A8	Pathogenic	no assertion criteria provided
1174596	NM_005629.4(SLC6A8):c.1016+2_1016+5del	SLC6A8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1308664	NM_005629.4(SLC6A8):c.1330G>T (p.Glu444Ter)	SLC6A8	Pathogenic	criteria provided, single submitter
1361089	NM_005629.4(SLC6A8):c.1169C>T (p.Pro390Leu)	SLC6A8	Pathogenic	reviewed by expert panel
1376685	NM_005629.4(SLC6A8):c.1283del (p.Gly428fs)	SLC6A8	Pathogenic	criteria provided, single submitter
1390569	NM_005629.4(SLC6A8):c.453_454insGCTGAGGCGGGAGAATCTCTTGAAGCCGGGAAGCAGAGGTTGCAGTGAACCGACATCGCGCCACTGCACTCCAGCCTGGGTGACAGAGTGAGACTCCATCTCAAAATAAATAAAAATAAAATAAAATAAAACAAGGTCTCATTCTCTTACCCAGGCTGGAGTGCAGTGGTACAATCAGAGCTCACCCCAGCCACAAACTCCTGGACTCAAGTGATCCTCCCACCTCAGCCTCCCTTGAATAGCTAGGACTACAAGTGTATGCCTCCAGGCCTGGCTAATTGTTTTTAATTTTTTGGTAGAGGCAGGGATCTCATTGTATTGCCCAGGCTGGGGTCCCAAACTCCTGATCACAAGTGAACCTCCTGCCTCAGCCTCTGAAAGTGCTGGGATTACAGGCATGAGCCACCGTGCCCAGCTCCCTGACAATTTCTGGCTGCATGGACTTCTGGTTACAAGCAGGGAAACTGAGGCCTGGATACAGCAAACAGGATCTGGCCCAGCTTTAAGTGGGGAACATGCAGTTTGGGGGACCCAGGCTCATGGTG (p.Leu152delinsAlaGluAlaGlyGluSerLeuGluAlaGlyLysGlnArgLeuGlnTer)	SLC6A8	Pathogenic	criteria provided, single submitter
1395238	NM_005629.4(SLC6A8):c.1496-1_1510del	SLC6A8	Pathogenic	criteria provided, single submitter
1397100	NM_005629.4(SLC6A8):c.444_445del (p.Ile149fs)	SLC6A8	Pathogenic	criteria provided, single submitter
1412467	NM_005629.4(SLC6A8):c.1055G>A (p.Ser352Asn)	SLC6A8	Pathogenic	criteria provided, single submitter
1416517	NM_005629.4(SLC6A8):c.1037_1038del (p.Leu346fs)	SLC6A8	Pathogenic	criteria provided, single submitter
1417554	NM_005629.4(SLC6A8):c.1210del (p.Ala404fs)	SLC6A8	Pathogenic	criteria provided, single submitter
1429550	NM_005629.4(SLC6A8):c.844del (p.Leu282fs)	SLC6A8	Pathogenic	criteria provided, single submitter
1679707	NM_005629.4(SLC6A8):c.627del (p.Val210fs)	SLC6A8	Pathogenic	criteria provided, single submitter
1686215	NM_005629.4(SLC6A8):c.980dup (p.Ser329fs)	SLC6A8	Pathogenic	criteria provided, single submitter
1687062	NM_005629.4(SLC6A8):c.1292_1302del (p.Asp431fs)	SLC6A8	Pathogenic	criteria provided, single submitter
1703957	NM_005629.4(SLC6A8):c.1519_1543del (p.Ile507fs)	SLC6A8	Pathogenic	reviewed by expert panel
1705030	NM_005629.4(SLC6A8):c.1548C>A (p.Cys516Ter)	SLC6A8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1706458	NM_005629.4(SLC6A8):c.1340_1341del (p.Val447fs)	SLC6A8	Pathogenic	criteria provided, multiple submitters, no conflicts
1802549	NM_005629.4(SLC6A8):c.1428C>G (p.Tyr476Ter)	SLC6A8	Pathogenic	reviewed by expert panel
1804054	NM_005629.4(SLC6A8):c.149dup (p.Pro51fs)	SLC6A8	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SLC6A8	Definitive	X-linked	creatine transporter deficiency	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC6A8	Orphanet:52503	X-linked creatine transporter deficiency
BCAP31	Orphanet:369939	Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome
BCAP31	Orphanet:369942	CADDS
ABCD1	Orphanet:139396	X-linked cerebral adrenoleukodystrophy
ABCD1	Orphanet:139399	Adrenomyeloneuropathy
ABCD1	Orphanet:369942	CADDS
ABCD1	Orphanet:388	Hirschsprung disease
ATP2B3	Orphanet:314978	X-linked non progressive cerebellar ataxia

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC6A8	HGNC:11055	ENSG00000130821	P48029	Sodium- and chloride-dependent creatine transporter 1	gencc,clinvar
BCAP31	HGNC:16695	ENSG00000185825	P51572	B-cell receptor-associated protein 31	clinvar
ABCD1	HGNC:61	ENSG00000101986	P33897	ATP-binding cassette sub-family D member 1	clinvar
ATP2B3	HGNC:816	ENSG00000067842	Q16720	Plasma membrane calcium-transporting ATPase 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC6A8	Sodium- and chloride-dependent creatine transporter 1	Creatine:sodium symporter which mediates the uptake of creatine.
BCAP31	B-cell receptor-associated protein 31	Functions as a chaperone protein.
ABCD1	ATP-binding cassette sub-family D member 1	ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen.
ATP2B3	Plasma membrane calcium-transporting ATPase 3	ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels at the presynaptic terminals.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	1	19.4×	0.151
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC6A8	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_creatine, SNS_sf
BCAP31	Other/Unknown	no		BAP29/BAP31, BAP29/BAP31_N, Bap31/Bap29_C
ABCD1	Transporter	yes	7.6.2.4	ABC_transporter-like_ATP-bd, AAA+_ATPase, FA_transporter
ATP2B3	Transcription factor	no	7.2.2.10	P_typ_ATPase, ATPase_P-typ_cation-transptr_N, ATPase_P-typ_cation-transptr_C

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	2
left adrenal gland	2
apex of heart	1
inferior olivary complex	1
right adrenal gland	1
right adrenal gland cortex	1
left adrenal gland cortex	1
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC6A8	291	ubiquitous	marker	inferior olivary complex, apex of heart, ileal mucosa
BCAP31	292	ubiquitous	marker	left adrenal gland, right adrenal gland, right adrenal gland cortex
ABCD1	201	ubiquitous	marker	ileal mucosa, left adrenal gland cortex, left adrenal gland
ATP2B3	145	tissue_specific	yes	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP2B3	3,203
BCAP31	3,085
SLC6A8	1,508
ABCD1	1,181

Intra-cohort edges

A	B	Sources
ABCD1	BCAP31	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCD1	P33897	14
SLC6A8	P48029	6
BCAP31	P51572	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP2B3	Q16720	74.57

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 45. Enrichment computed across 4 evidence-associated genes (4 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ABCD1 causes ALD	1	1427.5×	0.027	ABCD1
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	1	475.8×	0.027	ABCD1
Linoleic acid (LA) metabolism	1	285.5×	0.027	ABCD1
Creatine metabolism	1	259.6×	0.027	SLC6A8
Reduction of cytosolic Ca++ levels	1	237.9×	0.027	ATP2B3
Beta-oxidation of very long chain fatty acids	1	219.6×	0.027	ABCD1
alpha-linolenic acid (ALA) metabolism	1	178.4×	0.027	ABCD1
Platelet calcium homeostasis	1	178.4×	0.027	ATP2B3
Peroxisomal lipid metabolism	1	167.9×	0.027	ABCD1
ABC transporters in lipid homeostasis	1	150.3×	0.027	ABCD1
Class I peroxisomal membrane protein import	1	129.8×	0.027	ABCD1
Apoptotic cleavage of cellular proteins	1	119.0×	0.027	BCAP31
Apoptotic execution phase	1	119.0×	0.027	BCAP31
ABC transporter disorders	1	109.8×	0.027	ABCD1
Transport of small molecules	2	12.6×	0.027	ABCD1, ATP2B3
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	1	98.5×	0.028	BCAP31
Platelet homeostasis	1	69.6×	0.038	ATP2B3
Ion transport by P-type ATPases	1	51.9×	0.045	ATP2B3
Ion homeostasis	1	51.0×	0.045	ATP2B3
Respiratory Syncytial Virus Infection Pathway	1	49.2×	0.045	BCAP31
Protein localization	1	47.6×	0.045	ABCD1
Apoptosis	1	42.0×	0.048	BCAP31
RSV-host interactions	1	39.1×	0.050	BCAP31
Programmed Cell Death	1	36.6×	0.051	BCAP31
Disorders of transmembrane transporters	1	34.8×	0.051	ABCD1
Fatty acid metabolism	1	32.8×	0.052	ABCD1
ABC-family protein mediated transport	1	30.4×	0.052	ABCD1
Disease	2	6.5×	0.052	BCAP31, ABCD1
Cardiac conduction	1	27.2×	0.056	ATP2B3
Metabolism	2	5.8×	0.059	SLC6A8, ABCD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peroxisomal membrane transport	1	2106.5×	0.005	ABCD1
very long-chain fatty-acyl-CoA catabolic process	1	2106.5×	0.005	ABCD1
positive regulation of retrograde protein transport, ER to cytosol	1	1404.3×	0.005	BCAP31
positive regulation of unsaturated fatty acid biosynthetic process	1	1404.3×	0.005	ABCD1
creatine metabolic process	1	1053.2×	0.005	SLC6A8
creatine transmembrane transport	1	1053.2×	0.005	SLC6A8
sterol homeostasis	1	1053.2×	0.005	ABCD1
long-chain fatty acid import into peroxisome	1	842.6×	0.005	ABCD1
regulation of fatty acid beta-oxidation	1	702.2×	0.005	ABCD1
long-chain fatty acid catabolic process	1	702.2×	0.005	ABCD1
myelin maintenance	1	702.2×	0.005	ABCD1
regulation of mitochondrial depolarization	1	702.2×	0.005	ABCD1
calcium ion export across plasma membrane	1	702.2×	0.005	ATP2B3
fatty acid elongation	1	601.9×	0.005	ABCD1
very long-chain fatty acid catabolic process	1	601.9×	0.005	ABCD1
protein localization to endoplasmic reticulum exit site	1	526.6×	0.006	BCAP31
positive regulation of fatty acid beta-oxidation	1	383.0×	0.007	ABCD1
fatty acid derivative biosynthetic process	1	383.0×	0.007	ABCD1
regulation of cellular response to oxidative stress	1	324.1×	0.008	ABCD1
regulation of oxidative phosphorylation	1	300.9×	0.008	ABCD1
neuron projection maintenance	1	280.9×	0.008	ABCD1
negative regulation of reactive oxygen species biosynthetic process	1	247.8×	0.008	ABCD1
fatty acid homeostasis	1	234.1×	0.008	ABCD1
alpha-linolenic acid metabolic process	1	221.7×	0.008	ABCD1
positive regulation of ERAD pathway	1	221.7×	0.008	BCAP31
regulation of cardiac conduction	1	210.7×	0.009	ATP2B3
peroxisome organization	1	200.6×	0.009	ABCD1
very long-chain fatty acid metabolic process	1	191.5×	0.009	ABCD1
linoleic acid metabolic process	1	175.5×	0.009	ABCD1
unsaturated fatty acid biosynthetic process	1	162.0×	0.010	ABCD1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 3

Druggability breadth: 2 of 4 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC6A8	1	3
BCAP31	0	0
ABCD1	0	0
ATP2B3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CREATINE	3	SLC6A8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BCAP31	8	Binding:8
SLC6A8	1	Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABCD1	7.6.2.4	ABC-type fatty-acyl-CoA transporter
ATP2B3	7.2.2.10	P-type Ca2+ transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CREATINE	3	SLC6A8

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	SLC6A8
C	Druggable family + PDB, no drug	1	ABCD1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	BCAP31, ATP2B3

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BCAP31	8	—
ABCD1	0	—
ATP2B3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT06139172	Not specified	RECRUITING	Web Intervention for Parents of Youth With Genetic Syndromes (WINGS)
NCT06868979	Not specified	RECRUITING	Optical Imaging in X-linked Disorders.
NCT02931682	Not specified	TERMINATED	Observational Study of Males With Creatine Transporter Deficiency
NCT05642221	Not specified	COMPLETED	Functional Near-Infrared Spectroscopy (fNIRS) Combined With Diffuse Correlation Spectroscopy (DCS) in Neurocognitive Disease as Compared to Healthy Neurotypical Controls
NCT06292884	Not specified	UNKNOWN	Optical Imaging as a Tool for Monitoring Brain Function in Creatine Deficiency Syndromes