Optical Imaging as a Tool for Monitoring Brain Function in Creatine Deficiency Syndromes
The objective of this project is to explore the potential of functional near-infrared spectroscopy (fNIRS) as innovative functional biomarker for clinical trial readiness in Creatine Deficiency Syndromes (CDS), a group of rare neurodevelopmental disorders. Among these disorders, effective treatments are lacking for two. The limited availability of objective and quantitative biomarkers to monitor brain function poses challenges to advancing therapeutic research. With gene therapy trials on the horizon, the need for precise measurement to evaluate treatment efficacy is pressing. This project seeks to address this gap by assessing the prognostic reliability of both resting and task-evoked fNIRS. Arousal of participants will be also assessed through the measure of spontaneous heart rate (HR) fluctuations. The primary objectives of this pilot study are: 1. to determine the feasibility of fNIRS in individuals with CDS; 2. to collect pilot data on individuals with CDS to determine the patterns of cerebral oxygen consumption as measured by fNIRS; 3. to compare cerebral oxygen consumption changes at rest and from visual/auditory tasks in affected individuals versus age-appropriate healthy volunteers. The secondary objectives of this study are: 1. to correlate cerebral oxygen consumption changes from visual/auditory task in affected individuals to other measures of disease state (e.g., neuropsychological assessment, disease- specific severity rating scales); 2. to examine test-retest reliability of our fNIRS measures in both affected individuals and healthy controls.
- EligibilityCriteria: Inclusion Criteria:  CDS participants:  Age criteria: Between ages 2 years to 50 years old, inclusive at time of enrollment Diagnosed with either CTD or GAMT-D with a previously identified pathogenic or likely pathogenic variant in the SLC6A8 or GAMT gene. Must also meet the diagnostic criteria for CTD/GAMT-D. May be female or male  Typically developing participants:  Age criteria: Between ages 2 years to 50 years old, inclusive at time of enrollment Age- and sex-matched to the CDS participants No underlying genetic diagnosis or past/chronic medical condition associated with increased risk for autism spectrum disorder (ASD) and/or ID Typical neurodevelopment for age (no established diagnosis or clinical suspicion for ASD or ID)  Exclusion Criteria:  For CDS and Typically developing participants:  Unwilling or unable to comply with study procedures and assessments Contraindications to fNIRS, such as uncooperative or destructive behaviors preventing lead placement or capture by fNIRS equipment Traumatic loss of consciousness in the last year Has taken an investigational drug as part of another research study, within 30 days prior to study enrollment If participant is judged by the PI or Sub-I to be inappropriate for the study for any reason  For Typically developing participants:  Known or suspected cognitive impairment Known history of MRI abnormality Current use of psychotropic medications - HealthyVolunteers: Accepts Healthy Volunteers - Gender: All - MinimumAge: 2 Years - StdAgeList: Child, Adult, Older Adult - StudyPopulation: Creatine Deficiency Syndromes (CDS) are a family of three rare metabolic disorders (AGAT deficiency, AGAT-D, #602360, GAMT deficiency, GAMT-D, 601240 and Creatine Transporter Deficiency, CTD, #300352) negatively impacting brain development and its function. All CDS share a common, predominantly neurological, clinical presentation, including developmental delay, intellectual disabilities, disturbance of expressive and cognitive speech, psycho-motor impairment, autistic-like behavior, and seizures. Oral Cr supplementation leads to the attenuation of symptoms in AGAT-D patients, while for GAMT-D patients limited improvements can be achieved only at very high dosages. Effective treatments for CTD are completely missing as dietary supplementation with Cr, alone or in combination with its precursors, has very limited success. - SamplingMethod: Non-Probability Sample