Evaluation of Phenotypic Variability in Fabry Disease

Study Overview
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Brief Summary
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Cerebrovascular events, such as stroke, are a devastating complication of Fabry disease that results in part from storage of complex lipids in both large and small vessels. Understanding how the genotype influences the phenotype or clinical presentation can help us understand which patients are at risk for the complications of Fabry disease. This study aims to follow the natural history of this disease will help us understand and predict long-term outcomes for patients.

Detailed Description
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This longitudinal study will be conducted at Boston Children's Hospital (BCH). Subjects recruited for the study will have routine clinical care assessment with a complete physical and neurological exam and biochemical monitoring with venipuncture. In addition as part of the study, subjects will be given questionnaires to assess details of medical and psychosocial history, will complete self-reported measures of neuropsychological evaluation, pain scores, quality of life, executive functioning and cognitive functioning. All patients assessments will be repeated every 2 years.

Official Title
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Evaluation of Phenotypic Variability in Fabry Disease

Conditions
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Fabry Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who carry a classic alpha-galactosidase gene (GLA) mutation All ages Medical records available including previous genetic testing. Capable of providing informed consent with assent for patients less than 18 years Not currently involved in any other clinical trials. Exclusion Criteria: No medical records available No record of genotype Not capable of providing informed consent Currently involved in any clinical trial

Ages Eligible for Study
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Minimum Age: 1 Year

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 |
| --- | --- | --- |
| Globotriaosylceramide level, plasma | Biomarker for deficiency of alpha-galactosidase A (GLA) activity measured to determine if there are changes over time. | Data will be obtained and studied every 2 years for up to 10 years. | 
| Globotriaosylceramide level, urine | Biomarker for deficiency of alpha-galactosidase A (GLA) activity measured to determine if there are changes over time. | Data will be obtained and studied every 2 years for up to 10 years. | 
| Intelligence scale assessment | Wechsler Adult Intelligence Scale - Revised (WAIS-R) to assess for any changes in intelligence scale over time. | Data will be obtained and studied every 2 years for up to 10 years. | 
| Quality of life questionnaire | Single score based on questionnaire about quality of life to assess for any changes in scores over time. | Data will be obtained and studied every 2 years for up to 10 years. | 
| Executive functioning test | Single score based on testing of digit span backwards test, letter fluency, and category fluency to assess any changes in executive function over time. | Data will be obtained and studied every 2 years for up to 10 years. | 
| Pain questionnaire | Single score based on questionnaire about pain to evaluate progression of pain scores over time. | Data will be obtained and studied every 2 years for up to 10 years. | 
| Physical exam | Physical exam to evaluate for the development of angiokeratoma lesions and neurological symptoms development over time. | Data will be obtained and studied every 2 years for up to 10 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transcriptome analysis | High-throughput RNA sequencing will be done on plasma and peripheral blood lymphocytes to evaluate for changes over time. | Data will be obtained and studied every 2 years for up to 10 years. | 
| Metabolomic analysis | Comprehensive metabolite mapping of biochemical pathways to determine any metabolomic pathway changes in Fabry disease patients over time. | Data will be obtained and studied every 2 years for up to 10 years. | 
| Microbiome analysis | Optional stool sample will be obtained for microbiome analysis to detect the microbiome progression over time in Fabry disease patients. | Data will be obtained and studied every 2 years for up to 10 years. | 
| Targeted exome sequencing for evaluation of potential modifiers of Fabry disease phenotype. | Investigators will analyze sequencing results to determine the ability of whole exome sequencing to detect pathogenic modifiers of the Fabry disease phenotype. | Data will be obtained one time at initial study visit |