SLC13A5 Deficiency Natural History Study - Remote Only

Study Overview
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Brief Summary
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SLC13A5 deficiency (Citrate Transporter Disorder, EIEE 25) is a rare genetic disorder with neurodevelopmental delays and seizure onset in the first few days of life. This natural history study is designed to address the lack of understanding of disease progression and genotype-phenotype correlation. Additionally it will help in identifying clinical endpoints for use in future clinical trials.

Detailed Description
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This is a longitudinal observational study for the natural history of SLC13A5 deficiency for up to 2 years. This study does not involve any therapeutic intervention. The study includes remote visits which will be done via telephone or remote video conferencing. Translators will be available during these remote visits for non-english speaking caregivers. The initial visit will consist of collecting a detailed medical history and medical records. Prior brain imaging and available EEGs will be collected and reviewed by the study neurologist. Neuropsychological assessments will be made using Vineland Adaptive Behavior Scale version 3. Brief standardized videos recorded by the caregiver will be reviewed and scored by study personnel for movement assessment. Caregiver of ages 2 and up will be asked to complete the QOL Family Impact Module and the QOL epilepsy module. In addition to the initial visit, assessments in 1st year (every 3 months) and 2nd year (every 4 months) of enrollment will be made through remote interviews. Caregiver will be asked to maintain a seizure diary for the duration of the study to assess seizure burden. Personnel having expertise to comprehensively evaluate biological pathways that are perturbed by SLC13A5 deficiency will analyze the collected data. Improved understanding of disease pathogenesis will guide therapeutics and reveal clinical endpoints for use in future clinical trials. Identifying genotype-phenotype correlations can guide prognostication, clinical management, and genetic counseling.

Official Title
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SLC13A5 Deficiency: A Prospective Natural History Study - Remote Only (International)

Conditions
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Epilepsy, Citrate Transporter Deficiency, Rare Diseases, Movement Disorders, Genetic Disorder, SLC13A5 Deficiency, EIEE25, Kohlschutter-Tonz Syndrome (Non-ROGDI), 17p13.1 Deletions Confined to SLC13A5 Gene, Citrate Transporter Disorder

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parent(s)/legal representative and/or patient must be willing and able to give informed consent/assent for participation in the study. Males and females of any age are eligible for this study Suspected or confirmed diagnosis of SLC13A5 deficiency with genetic variants in both SLC13A5 alleles and consistent clinical characteristics. Variants of uncertain significance in one or both alleles are acceptable if deemed good candidates by participant's primary geneticist or neurologist and study personnel. Participant and caregiver must be willing to provide clinical data and participate in standardized assessments. Exclusion Criteria: 1. The presence of a second, confirmed disorder, genetic or otherwise, affecting neurodevelopment or with other overlapping symptoms of SLC13A5 deficiency. -
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SLC13A5 deficiency motor scale assessments. | Caregiver will be asked to record brief standardized videos capturing the degree of disordered movements. These videos will be made and reviewed for all assessment sessions. Different movements/tasks will be assessed on different scales ranging from 0 to 8. Lesser scores represent better outcome. | Upto 24 months | 
| Developmental assessment at baseline and longitudinally using Vineland 3 | The Vineland Adaptive Behavior Scales, Third Edition (Vineland 3) provides a comprehensive assessment of adaptive function and has been widely used in populations with intellectual and developmental disabilities. It is validated from birth to 90 years, and scores abilities across three core and two optional domains: communication, daily living skills, socialization, and motor skills and maladaptive behaviors, respectively. Completion time for the comprehensive interview is estimated at 50 minutes when all five domains are included. Reliability and validity are widely established. Vineland 3 Adaptive Behavior Scale questionnaire will be included in the remote interviews during the initial visit for baseline assessment and followed at 6 months, 12 months and 24 months for longitudinal neuropsychological assessment | Upto 24 months | 
| Seizure burden and semiology | Caregiver will be asked to log number and type of seizures for the 4 weeks prior to each remote interview in a seizure tracker form. Reportable seizure types are to include: simple partial seizures (focal onset with retained awareness) WITHOUT motor signs, simple partial seizures WITH motor signs, complex partial seizures (focal onset with impaired awareness), partial (focal) seizures with secondary generalization, absences, myoclonic seizures, clonic seizures, tonic seizures, atonic seizures, and generalized tonic-clonic seizures. In addition, to assess overall change in seizure burden in 4 months between the remote interviews, Seizure Global Impression of Change (Seizure GIC) will be filled at all the remote interviews. Caregiver global impression of change will be assessed using a seven-point Likert scale. In addition, caregiver impression of change in seizure frequency and duration will be assessed using a three-point Likert scale. | Upto 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Caregiver Quality of Life (QOL) | Caregiver of patients of ages 2 and up will be asked to fill questionnaires related to PedsQL Family Impact Module and PedsQL Caregiver Epilepsy Module in the initial visit and thereafter at 6 months, 12 months and 24 months. PedsQL Family Impact Module assess the impact of pediatric chronic health conditions on parents/caregiver and family by measuring parent/caregiver self-reported physical, emotional, social, and cognitive functioning, communication, and worry. The PedsQL Epilepsy Module is a 29-item measure with five scales: Impact, Cognitive, Sleep, Executive Function, and Mood/Behavior. The Impact Scale assesses how epilepsy disrupts daily activities, interacting with peers, independence, and increased disease burden due to treatment. | Upto 24 months | 
| Sleep disturbances scale for children (SDSC) | Caregiver will be asked to fill a one-page questionnaire to assess dependents disorders of sleep. The Sleep Disturbance Scale for Children (SDSC) is a 27-item inventory rated on a 5 point Likert-type scale. The instrument's purpose is to categorize sleep disorders in children. As well as giving an overall score the instrument uses five subdomains: disorders of initiating and maintaining sleep, sleep breathing disorders, disorders of arousal, sleep-wake transition disorders, disorders of excessive somnolence, and sleep hyperhidrosis. | Upto 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Rare Disease, Movement Disorders, Genetic Disorder, Citrate Transporter Disorder, SLC13A5 Deficiency, EIEE25, Neonatal seizures, autosomal recessive