Relevant Outcome Measures for Creatine Transporter Deficiency Patient

Study Overview
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Brief Summary
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Creatine transport deficiency (CTD) is a rare genetic disorder related to pathogenic variants in the SLC6A8 gene, located on chromosome Xq28. Clinical diagnosis of CTD is based on clinical presentation, an increased urinary creatine/creatinine ratio and a severe decreased creatine peak on 1H-MRS magnetic resonance spectroscopy. A retrospective study with questionnaires identified that most CTD patients had moderate to severe intellectual disability. Less than one third of patients were able to speak in sentences. Seizures were present in 59% of the patients. 41% had autistic features. Motor dysfunction was mentioned in 58%, and gastrointestinal symptoms were reported in 35% of the patients. Several new therapeutic avenues are currently emerging in this disease for which no treatment has been available until now : cyclocreatine (interesting but unfortunately with very little clinical applicability due to its toxicity; dodecyl creatine ester incorporated into lipid nanocapsules with intranasal administration; pharmaco-chaperoning (for the folding-deficient creatine transporter variants, Ultragenyx pharmaceuticals new prodrug designed to deliver creatine to the brain (UX068). These new pharmacological treatment options may offer future opportunities to improve cognition in CTD patients. A key issue is to determine outcome measures that are accessible to these patients, despite the importance of their cognitive deficit. In a preliminary study (on 31 CTD patients), investigators showed for example, that 75% of patients were unable to perform a Wechsler scale, which is one of the most used neuropsychological test to determine patient IQ (intelligence quotient). Most of the existing cognitive tests were developed to distinguish typically developing persons and ID (intellectual disability) patients, leading to a floor effect in the latter who systematically fail these tests. Therefore, these tests are not adapted to capture the potential effect of a drug in ID patient group. The identification of reliable and sensitive outcome measures for use in clinical trials in ID patients was recognized as a priority in a meeting convened by the NIH. N-of-1 trials (also called Single-Case Experimental Designs or SCEDs) appear of great interest for rare diseases, statistical power coming from the number of repeated measures, which leads to choose outcome measures that can be repeated multiple times. This innovative study will allow to efficiently preparing future therapeutic trials, by specifying the phenotype of the patients, and by determining the most adapted outcome measures taking into account their cognitive deficiency and the type of experimental design to be used in the context of rare diseases.

Official Title
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A Prospective Study in Creatine Transporter Deficiency (SLC6A8) Patients to Determine the Most Relevant Outcome Measures

Conditions
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Creatine Transporter Defect

Intervention / Treatment
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* Other: Clinical endpoints
* Other: Parental questionnaires
* Other: Quality of life scale
* Other: Cognitive assessments
* Other: Language assessments
* Other: Motor assessments
* Other: Social assessments
* Other: 3T MRI
* Other: Cardiac assessments
* Other: Biological collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CTD patients (n=24) Male CTD patients Having a confirmed mutation in the SLC6A8 gene, Aged > 5 to < 35 years Whose maternal language is French, Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent, Affiliated to national Health Insurance system or parents/legal guardian affiliated to national health insurance system. Sex- and chronological age-matched controls (n=24) Male Aged > 5 to < 35 years Whose maternal language is French, Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent, Affiliated to national health insurance system or parents/legal guardian affiliated to national health insurance system. Sex- and mental age-matched controls (n=24) Male Aged > 3 to < 8 years Whose maternal language is French, For whom parents/legal guardian have signed the informed consent, Affiliated to national health insurance system or parents/legal guardian affiliated to national health insurance system. Typically developed children (n=80) Male and female Aged > 3 to < 8 years Whose maternal language is French, For whom parents/legal guardian have signed the informed consent, Affiliated to national health insurance system or parents/legal guardian affiliated to national health insurance system. Exclusion Criteria: CTD patients (n=24): Having a contraindication to the MRI examination (people using a pacemaker or an insulin pump, people wearing a metal prosthesis or an intracerebral clip, and claustrophobic subjects), Refusal of the subject and/or the subject's parents to be informed of possible abnormalities detected by MRI, Refusal of the subject and/or the subject's parents/legal guardian to be informed of possible abnormalities detected during the cardiac assessment. Sex- and chronological age-matched controls (n=24) History of neurological or psychiatric disorder, Repetition of a grade, Learning disability requiring rehabilitation (speech therapy, psychomotor or oculomotor therapy), For participants agreeing on performing the MRI examination, having a contraindication to the MRI examination (use of a pacemaker or an insulin pump, people wearing a metal prosthesis or an intracerebral clip, and claustrophobic subjects) and refusal of the subject and/or the subject's parents/legal guardian to be informed of possible abnormalities detected by MRI. Sex- and mental age-matched controls (n=24) History of neurological or psychiatric disorder, Repetition of a grade, Learning disability requiring rehabilitation (speech therapy, psychomotor or oculomotor therapy). Typically developed children (n=80) History of neurological or psychiatric disorder, Repetition of a grade, Learning disability requiring rehabilitation (speech therapy, psychomotor or oculomotor therapy).

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: CTD patients<br>Case group 24 male CTD patients having a confirmed mutation in the SLC6A8 gene, aged > 5 to < 35 years. | Other: Clinical endpoints<br>* Number of epileptic seizures Change in antiepileptic treatment (increase or decrease) Visual analogical scale on a target symptom defined with the parents, CGI, Actimetry data over 24 hours, Podometry data over 24 hours, 6 minutes' walk test, Clinical examination Feasibility of performing an MRI without any anesthesia on a mock scanner<br>Other: Parental questionnaires<br>* 10- Adaptive assessment with Vineland Adaptive Behavior scale II, 11- Mac Arthur questionnaire regarding language, 12- Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS), 13- Dunn sensory profile, 14- Aberrant Behavior Checklist, 15- Nisonger Child Behavior Rating form, 16- Social Responsiveness Scale 2, 17- Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)<br>Other: Quality of life scale<br>* 18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)<br>Other: Cognitive assessments<br>* 19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible 20- CPM-BF 21- Simple reasoning task on tablet (match-to-sample task) 22- Implicit rules learning (modified Brixton), 23- 4 sub-tests from the WPPSI-IV (zoo location to assess spatial memory, block design to assess visuo-constructive abilities, bug search , cancellation), 24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention), 25- Elementary visuo-spatial perception (on tablets)<br>Other: Language assessments<br>* 26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments), 27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary), 28- Automatic language analysis (during a 10 minutes interaction, play).<br>Other: Motor assessments<br>* 29- Kinematic task (specifically designed), 30- Purdue-Pegboard test, 31- Renzi test<br>Other: Social assessments<br>* 32- Eye-tracking analysis of social visual scenes and social preference index (movies), 33- theory of mind assessment, 34- ADOS scale (Autism Spectrum Disorder), 35- sensitivity to inequality, 36- pro-social behaviors (help of the psychologist)<br>Other: 3T MRI<br>* 37- Structural, metabolic and functional data<br>Other: Cardiac assessments<br>* 38- ECG 39- Ultrasound<br>Other: Biological collection<br>* 40- Blood sample 41- Urinary sample 42- Superficial skin biopsy<br>|
| Other: Sex and chronological age matched controls<br>Control group 24 male, sex and chronological age matched controls, aged > 5 to < 35 years | Other: Clinical endpoints<br>* Number of epileptic seizures Change in antiepileptic treatment (increase or decrease) Visual analogical scale on a target symptom defined with the parents, CGI, Actimetry data over 24 hours, Podometry data over 24 hours, 6 minutes' walk test, Clinical examination Feasibility of performing an MRI without any anesthesia on a mock scanner<br>Other: Quality of life scale<br>* 18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)<br>Other: Cognitive assessments<br>* 19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible 20- CPM-BF 21- Simple reasoning task on tablet (match-to-sample task) 22- Implicit rules learning (modified Brixton), 23- 4 sub-tests from the WPPSI-IV (zoo location to assess spatial memory, block design to assess visuo-constructive abilities, bug search , cancellation), 24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention), 25- Elementary visuo-spatial perception (on tablets)<br>Other: Language assessments<br>* 26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments), 27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary), 28- Automatic language analysis (during a 10 minutes interaction, play).<br>Other: Motor assessments<br>* 29- Kinematic task (specifically designed), 30- Purdue-Pegboard test, 31- Renzi test<br>Other: Social assessments<br>* 32- Eye-tracking analysis of social visual scenes and social preference index (movies), 33- theory of mind assessment, 34- ADOS scale (Autism Spectrum Disorder), 35- sensitivity to inequality, 36- pro-social behaviors (help of the psychologist)<br>Other: 3T MRI<br>* 37- Structural, metabolic and functional data<br>|
| Other: Sex and mental age matched controls<br>Control group 24 male, sex and mental age matched controls, aged > 3 to < 8 years | Other: Parental questionnaires<br>* 10- Adaptive assessment with Vineland Adaptive Behavior scale II, 11- Mac Arthur questionnaire regarding language, 12- Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS), 13- Dunn sensory profile, 14- Aberrant Behavior Checklist, 15- Nisonger Child Behavior Rating form, 16- Social Responsiveness Scale 2, 17- Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)<br>Other: Quality of life scale<br>* 18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)<br>Other: Cognitive assessments<br>* 19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible 20- CPM-BF 21- Simple reasoning task on tablet (match-to-sample task) 22- Implicit rules learning (modified Brixton), 23- 4 sub-tests from the WPPSI-IV (zoo location to assess spatial memory, block design to assess visuo-constructive abilities, bug search , cancellation), 24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention), 25- Elementary visuo-spatial perception (on tablets)<br>Other: Language assessments<br>* 26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments), 27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary), 28- Automatic language analysis (during a 10 minutes interaction, play).<br>Other: Motor assessments<br>* 29- Kinematic task (specifically designed), 30- Purdue-Pegboard test, 31- Renzi test<br>Other: Social assessments<br>* 32- Eye-tracking analysis of social visual scenes and social preference index (movies), 33- theory of mind assessment, 34- ADOS scale (Autism Spectrum Disorder), 35- sensitivity to inequality, 36- pro-social behaviors (help of the psychologist)<br>|
| Other: Typically developed children<br>Control group 80 typically developed children aged > 3 to < 8 years, which corresponds to the mental age of CTD patients. 40 children aged > 3 to < 5 years, and 40 children aged > 6 to < 8 years will perform the newly developed outcome measures. | Other: Parental questionnaires<br>* 10- Adaptive assessment with Vineland Adaptive Behavior scale II, 11- Mac Arthur questionnaire regarding language, 12- Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS), 13- Dunn sensory profile, 14- Aberrant Behavior Checklist, 15- Nisonger Child Behavior Rating form, 16- Social Responsiveness Scale 2, 17- Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)<br>Other: Quality of life scale<br>* 18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)<br>Other: Cognitive assessments<br>* 19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible 20- CPM-BF 21- Simple reasoning task on tablet (match-to-sample task) 22- Implicit rules learning (modified Brixton), 23- 4 sub-tests from the WPPSI-IV (zoo location to assess spatial memory, block design to assess visuo-constructive abilities, bug search , cancellation), 24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention), 25- Elementary visuo-spatial perception (on tablets)<br>Other: Language assessments<br>* 26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments), 27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary), 28- Automatic language analysis (during a 10 minutes interaction, play).<br>Other: Motor assessments<br>* 29- Kinematic task (specifically designed), 30- Purdue-Pegboard test, 31- Renzi test<br>Other: Social assessments<br>* 32- Eye-tracking analysis of social visual scenes and social preference index (movies), 33- theory of mind assessment, 34- ADOS scale (Autism Spectrum Disorder), 35- sensitivity to inequality, 36- pro-social behaviors (help of the psychologist)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical endpoints : number of epileptic seizures | Number of epileptic seizures | Up to 90 Days | 
| Clinical endpoints : antiepileptic treatment | Change in antiepileptic treatment (increase or decrease) | For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). | 
| Clinical endpoints : Visual analogical scale | Visual analogical scale on a target symptom defined with the parents, | Up to 90 Days | 
| Clinical endpoints : actimetry | Actimetry data over 48 hours | Up to 90 Days | 
| Clinical endpoints : podometry | Podometry data over 24 hours | Up to 90 Days | 
| Clinical endpoints : walk test | 6 minutes' walk test | Up to 90 Days | 
| Clinical endpoints : Clinical examination | Clinical examination | For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). | 
| Clinical endpoints :Feasibility of performing an MRI | Feasibility of performing an MRI without any anesthesia on a mock scanner | For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). | 
| Parental questionnaires : Vineland Adaptive Behavior scale II | Adaptive assessment with Vineland Adaptive Behavior scale II | For all 24 CTD patients: V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90). | 
| Parental questionnaires : Mac Arthur questionnaire | Mac Arthur questionnaire regarding language | For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). | 
| Parental questionnaires : PDD-MRS | Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS) | For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90). | 
| Parental questionnaires : Dunn sensory profile | Dunn sensory profile | For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). | 
| Parental questionnaires : Aberrant Behavior Checklist | Aberrant Behavior Checklist | For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). | 
| Parental questionnaires : Nisonger Child Behavior Rating form | Nisonger Child Behavior Rating form | For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90). | 
| Parental questionnaires : Social Responsiveness Scale 2 | Social Responsiveness Scale 2 | For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90). | 
| Parental questionnaires : impact on primary caregiver | Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL) | For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). | 
| Quality of life scale | Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18) | For all 24 CTD patients: At V1 (Day1/Day2) For 9 out of 24 CTD patients: Repeated at V3 (Day30) and V7 (Day90). | 
| Cognitive assessments : Leiter 3 scale | Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible | For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1) | 
| Cognitive assessments : CPM-BF | CPM-BF : Raven's coloured Progressive Matrices | For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1) | 
| Cognitive assessments : reasoning task | Simple reasoning task on tablet (match-to-sample task) | For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1) | 
| Cognitive assessments : Implicit rules learning | Implicit rules learning (modified Brixton), | For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1) | 
| Cognitive assessments : WPPSI-IV | 4 sub-tests from the WPPSI-IV (zoo location to assess spatial memory, block design to assess visuo-constructive abilities, bug search , cancellation), | For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1) | 
| Cognitive assessments : Attention assessment | Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention), | For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1) | 
| Cognitive assessments : Elementary visuo-spatial perception | Elementary visuo-spatial perception (on tablets) | For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1) | 
| Language assessments : EXALANG 3-6 | EXALANG 3-6 - Computerized battery for the evaluation of oral and written language : 10 sub-tests testing for expressive and receptive language assessments | For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1) | 
| Language assessments : vocabulary | PPVT-5 : Peabody Picture Vocabulary Test Fifth Edition = receptive vocabulary, EVT-3 : Expressive Vocabulary Test third edition, | For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1) | 
| Language assessments : Automatic language analysis | Automatic language analysis (during a 10 minutes interaction, play). | For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1) | 
| Motor assessments : Kinematic task | Kinematic task (specifically designed) | CTD patients : performed at V1 (Day1/Day2). Controls: Motor assessment at V1 (Day 1) | 
| Motor assessments : Purdue-Pegboard test | Purdue-Pegboard test | CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1) | 
| Motor assessments : Renzi test | Renzi test | CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1) | 
| Social assessments : Eye-tracking | Eye-tracking analysis of social visual scenes and social preference index (movies) | CTD patients : performed at V1 (Day1/Day2), V3 (Day30) and V7 (Day90). Controls : Social assessment at V1(Day1) | 
| Social assessments : Theory of mind assessment | Theory of mind assessment | CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1) | 
| Social assessments : ADOS scale (Autism Diagnostic Observation Scale) | ADOS scale (Autism Spectrum Disorder) | CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1) | 
| Social assessments : Sensitivity to inequality | Sensitivity to inequality | CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1) | 
| Social assessments : Pro-social behaviors (help of the psychologist) | Pro-social behaviors (help of the psychologist) | CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuroimaging (MRI) | The MRI will be performed to describe structural and functional neuroanatomical profile of CTD patient in comparison to chronological age-matched controls and variability in creatine peak assessment using MR spectroscopy | V1 (Day1/Day2) | 
| Cardiac assessments : Electrocardiogram | Electrocardiogram (ECG) will be performed to describe CTD patients cardiac profile (especially the risk of increased QTC and/or cardiac echography abnormality) | CTD patients: V1 (Day1/Day2) | 
| Cardiac assessments : Ultrasound | Cardiac Ultrasound will be performed to describe CTD patients cardiac profile (especially the risk of increased QTC and/or cardiac echography abnormality) | CTD patients: V1 (Day1/Day2) | 
| Biological collection : Blood sample | Blood sample (plasma and peripheral blood mononuclear cells) | CTD patients: V1 (Day1/Day2) | 
| Biological collection : Urine sample | Urine sample will be collected to create a collection of biological samples associated with clinical and genomic data from CTD patients. In the future this will be usefull for research labs to investigate new biomarkers (not identified yet) or to test for the efficiency of new therapeutic approaches in vitro (on cultivated fibroblasts or after the development of iPS cells or organoïds) in this rare disease. | CTD patients: V1 (Day1/Day2) | 
| Biological collection : Superficial skin biopsy | Superficial skin biopsy will be performed to get cultivated fibroblasts to create a collection of biological samples associated with clinical and genomic data from CTD patients. In the future this will be usefull for research labs to investigate new biomarkers (not identified yet) or to test for the efficiency of new therapeutic approaches in vitro (on cultivated fibroblasts or after the development of iPS cells or organoïds) in this rare disease. | CTD patients: V1 (Day1/Day2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Creatine Transporter Deficiency (SLC6A8), Outcome measures, Therapeutics, Feasibility, Relevance