Registry of X-linked Adrenoleukodystrophy

Study Overview
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Brief Summary
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This study is a observational study conducted through recruiting X-linked adrenoleukodystrophy (X-ALD) patients, to build a comprehensive evaluation and long-term follow-up platform for X-ALD patients, and to provide a theoretical basis for the treatment and management of X-ALD patients.

Detailed Description
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In this study, X-ALD patients will be selected as study participants. Through a longitudinal collection of genetic, imaging and clinical symptoms data of the patients and carriers. The purpose of this study is to build a comprehensive evaluation and long-term follow-up platform for X-ALD patients. Through the long-term follow-up of imaging and clinical symptoms progress and outcome of X-ALD patients, combined with genetic data, we will improve the relationships between genes and phenotypes, and explore the deep insight in the pathophysiological mechanism of X-ALD, to provide a theoretical basis for the treatment and management of X-ALD patients.

Official Title
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Registry of X-linked Adrenoleukodystrophy

Conditions
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X-linked Adrenoleukodystrophy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: X-ALD group： Meet the diagnostic criteria of X-ALD and supported by the results of genetic and very long chain fatty acid (VLCFA) test; Age: 6 - 70 years old; Able to communicate normally, and complete the test of scale as instructed (confirmed by the field test of scale); Sign the informed consent. Carrier-control group: Healthy people who have no significant difference in age, sex and education comparing with the X-ALD group, volunteer to participate in this study, could complete the test of scale as instructed, and meet the following criteria: Eligible for asymptomatic carriers in genetic tests (preference of patient's mother and close relatives); Age: 6 - 70 years old, able to complete the test of scale as instructed (confirmed by the field test of scale); No history of psychiatric diseases. Exclusion Criteria: Other hereditary diseases; Other severe central nervous diseases; History of surgery of brain or eye; Psychiatric and psychological diseases, such as anxiety and depression; Metal foreign body or prosthesis in the human body (such as pacemaker and insulin pump), claustrophobia, and other MRI contraindications; History of surgery associated with gastrointestinal tract; No informed consent; Unable to tolerate MRI or eye related tests.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 70 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| X-ALD<br>X-linked adrenoleukodystrophy (X-ALD) patients. | |
| Carrier-control (CC)<br>Carriers of mutation in gene encoding ATP-binding cassette subfamily D member 1 (ABCD1), who have no X-linked adrenoleukodystrophy and are matched with the X-ALD group according to age, sex and education. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epidemiological characteristics in Chinese X-ALD patients | Constructing a Chinese X-ALD epidemiological information database by collecting epidemiological information from X-ALD patients. | 5 years | 
| Clinical characteristics in Chinese X-ALD patients | Constructing a Chinese X-ALD clinical sympotoms information database by collecting clinical symptoms information from X-ALD patients. | 5 years | 
| Imaging characteristics in Chinese X-ALD patients | Constructing a Chinese X-ALD patient's head MRI information database by collecting head MRI information from X-ALD patients. | 5 years | 
| The disease development in Chinese X-ALD patients | Record the progress of patients' clinical symptoms from baseline through 5-year follow-up. | 5 years | 
| New pathogenic loci of Chinese X-ALD patients in whole genome sequencing/whole exon sequencing | To find and identify new pathogenic loci of X-ALD in whole genome sequencing/whole exon sequencing through comparing the differences of whole genome sequencing/whole exon sequencing between X-ALD patients and carrier-control individuals. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Etiology of Chinese X-ALD patients | Etiological factors,including genetic and environmental etiological factors, will be explored by genomic analysis, lasso regression, multiple logistic regression, and cox proportional hazards regression. | 5 years | 
| The change of imagin features in Chinese X-ALD patients | Record the change of the patient's head MRI from baseline through follow-up every year. | day 1, year 1, year 2, year 3, year 4, year 5 | 
| The associations between genetic factors and clinical characteristics of Chinese X-ALD patients | β coefficient and 95%CI values in linear regression, OR and 95%CI values in logistic regression analysis, and HR and 95%CI values in cox proportional hazards regression analysis for the associations between genetic factors and clinical characteristics of X-ALD. | 5 years | 
| The associations between genetic factors and outcomes of Chinese X-ALD patients | β coefficient and 95%CI values in linear regression, OR and 95%CI values in logistic regression analysis, and HR and 95%CI values in cox proportional hazards regression analysis for the associations between genetic factors and outcomes of X-ALD. | 5 years | 
| The associations between genetic factors and imaging characteristics of Chinese X-ALD patients | β coefficient and 95%CI values in linear regression, OR and 95%CI values in logistic regression analysis, and HR and 95%CI values in cox proportional hazards regression analysis for the associations between genetic factors and imaging characteristics of X-ALD. | 5 years | 
| The associations between genetic factors and the long-term changes of imaging characteristics of Chinese X-ALD patients | β coefficient and 95%CI values in linear regression, OR and 95%CI values in logistic regression analysis, and HR and 95%CI values in cox proportional hazards regression analysis for the associations between genetic factors and the long-term changes of imaging characteristics of X-ALD. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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X-linked Adrenoleukodystrophy, Genetic data, Phenotype, Imaging feature, Mechanism