Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)

Study Overview
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Brief Summary
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The Peroxisome Biogenesis Disorders (PBD) are a group of inherited disorders due to defects in peroxisome assembly causing complex developmental and metabolic sequelae. In spite of advancements in peroxisome biology, the pathophysiology remains unknown, the spectrum of phenotypes poorly characterized and the natural history not yet systematically reported. Our aims are to further define this population clinically, biochemically and genetically. The investigators will prospectively follow patients from Canada, the US and internationally, and collect data from medical evaluations, blood, urine and imaging studies that would be performed on a clinical care basis. For patients who are unable to attend our clinic, we will collect all medical records and images since birth as well as subsequent records/images for the next 5 years or until the end of the study. Clinical data from medical records will be banked in our Peroxisomal Disorder Research Databank and Biobank. The investigators will use this information to identify standards of care and improve management.

Detailed Description
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Participants have the option to be seen in consultation at the McGill University Health Centre in Montreal, Canada, on a yearly basis. This includes a consultation in Genetics, Nutrition, Neurology, and Ophthalmology (OCT and FAF exams). All medical records and images will be collected, retrospectively and prospectively, until the end of the study, and entered anonymously in a database. Biospecimens will be collected to identify new biomarkers. Candidate drugs will be evaluated for recovery of peroxisome functions in cultured fibroblasts.

Official Title
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Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)

Conditions
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Peroxisome Biogenesis Disorder, Zellweger Spectrum Disorder, RCDP - Rhizomelic Chondrodysplasia Punctata, D-Bifunctional Protein Deficiency, Alpha-Methylacyl-CoA Racemase Deficiency, Peroxisomal Acyl-CoA Oxidase Deficiency, Peroxisomal Acyl-CoA Oxidase 2 Deficiency, ATP Binding Cassette Subfamily D Member 3 Gene Mutation, ACBD5 (AcylCoA Binding Domain 5) Deficiency, Adult Refsum Disease, Sterol Carrier Protein 2 Deficiency

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PBD or Single peroxisome enzyme/protein defect with phenotype similar to PBD Exclusion Criteria: Not a PBD Not a single peroxisome enzyme/protein defect with phenotype similar to PBD
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients diagnosed with a peroxisomal disorder<br>Collection of medical records and images (ultrasounds, X-rays, MRIs, CT scans, ophthalmic images), Next-generation panel, Drug screening, and Consultation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Documentation of the clinical findings | Clinical findings include but are not limited to: life span, growth parameters, development, vision, hearing, neurological examinations, renal problems, adrenal function, skeletal problems, and any other system involvement. | Yearly up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peroxisome function testing | To include very long chain saturated, branched and polyunsaturated fatty acids, bile acids, plasmalogens, pipecolic acid, adrenal functions, liver functions, and urine oxalate. | Yearly up to 10 years | 
| Development of leukodystrophy | Identification of patterns and course by MRI | Yearly up to 10 years | 
| Scoring of fundus photography (OCT and FAF) | Identification of patterns and course | Yearly up to 10 years | 
| Genotype-phenotype correlation | Correlation of mutation type to peroxisome biochemistry, number and type of disease complications. | Yearly up to 10 years | 
| Frequency of various disease complications and identification of risk factors in the PBD population | Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones | Yearly up to 10 years | 
| Development of care management guideline resource for adolescents and adults with PBD-ZSD | Medical issues (Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones), main challenges, and the pediatric-to-adult transition experience will be included in PBD-ZSD adult-specific management guidelines | Yearly up to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peroxisome biogenesis disorders, PBD, Zellweger spectrum disorder, Rhizomelic chondrodysplasia punctata, DBP, ACOX1, AMACR, ARD, ACBD5, ZSD, RCDP, ACOX2, ABCD3, Adult Refsum, PHYH, SCPx, RCDP1, RCDP2, RCDP3