Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)
Study Details
Study Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Patients diagnosed with a peroxisomal disorder Collection of medical records and images (ultrasounds, X-rays, MRIs, CT scans, ophthalmic images), Next-generation panel, Drug screening, and Consultation |
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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
- Genotype-phenotype correlation [Yearly up to 10 years]
Correlation of mutation type to peroxisome biochemistry, number and type of disease complications.
- 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
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Institute of the McGill University Health Center | Montreal | Quebec | Canada | H4A 3J1 |
Sponsors and Collaborators
- McGill University Health Centre/Research Institute of the McGill University Health Centre
Investigators
- Principal Investigator: Nancy E Braverman, MD, MS, McGill University Health Center, Montreal Childrens Hopital
Study Documents (Full-Text)
None provided.More Information
Publications
- Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M. Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab. 2016 Mar;117(3):313-21. doi: 10.1016/j.ymgme.2015.12.009. Epub 2015 Dec 23. Review.
- Braverman NE, Steinberg SJ, Fallatah W, Duker A, Bober M. Rhizomelic Chondrodysplasia Punctata Type 1. 2001 Nov 16 [updated 2020 Jan 30]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK1270/
- Rush ET, Goodwin JL, Braverman NE, Rizzo WB. Low bone mineral density is a common feature of Zellweger spectrum disorders. Mol Genet Metab. 2016 Jan;117(1):33-7. doi: 10.1016/j.ymgme.2015.11.009. Epub 2015 Nov 24.
- Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK1448/
- Wangler MF, Hubert L, Donti TR, Ventura MJ, Miller MJ, Braverman N, Gawron K, Bose M, Moser AB, Jones RO, Rizzo WB, Sutton VR, Sun Q, Kennedy AD, Elsea SH. A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers. Genet Med. 2018 Oct;20(10):1274-1283. doi: 10.1038/gim.2017.262. Epub 2018 Feb 8.
- 11-090-PED