ACBD5 (AcylCoA Binding Domain 5) Deficiency, Adult Refsum Disease, Alpha-Methylacyl-CoA Racemase Deficiency, ATP Binding Cassette Subfamily D Member 3 Gene Mutation, D-Bifunctional Protein Deficiency, Peroxisomal Acyl-CoA Oxidase 2 Deficiency, Peroxisomal Acyl-CoA Oxidase Deficiency, Peroxisome Biogenesis Disorder, RCDP - Rhizomelic Chondrodysplasia Punctata, Sterol Carrier Protein 2 Deficiency, Zellweger Spectrum Disorder
Conditions
Keywords
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
Brief summary
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
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.
Interventions
None listed
Sponsors
McGill University Health Centre/Research Institute of the McGill University Health Centre
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Documentation of the clinical findings | Yearly up to 10 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Development of leukodystrophy | Yearly up to 10 years | Identification of patterns and course by MRI |
| Scoring of fundus photography (OCT and FAF) | Yearly up to 10 years | Identification of patterns and course |
| Peroxisome function testing | Yearly up to 10 years | To include very long chain saturated, branched and polyunsaturated fatty acids, bile acids, plasmalogens, pipecolic acid, adrenal functions, liver functions, and urine oxalate. |
| Frequency of various disease complications and identification of risk factors in the PBD population | Yearly up to 10 years | Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones |
| Development of care management guideline resource for adolescents and adults with PBD-ZSD | Yearly up to 10 years | 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 |
| Genotype-phenotype correlation | Yearly up to 10 years | Correlation of mutation type to peroxisome biochemistry, number and type of disease complications. |
Countries
Canada
Contacts
Primary ContactNancy E Braverman, MD, MS
Backup ContactEvelyn M Zavacky, MSc
Outcome results
None listed