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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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Any patient with a PBD diagnosis- or related single enzyme/protein defect
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nancy E Braverman, MD, MS | Contact | (1) 514-934-1934 | 23404 | nancy.braverman@mcgill.ca |
| Evelyn M Zavacky, MSc | Contact | (1) 514-934-1934 | 23403 | pbd.genetics@mcgill.ca |
| Name | Affiliation | Role |
|---|---|---|
| Nancy E Braverman, MD, MS | McGill University Health Center, Montreal Childrens Hopital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Institute of the McGill University Health Center | Recruiting | Montreal | Quebec | H4A 3J1 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20301621 | Background | Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1448/ | |
| 26750748 |
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blood, dried blood spots, urine, and specimens obtained for other e.g. cultured fibroblasts, liver biopsies
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 |
| 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. |
| 20301447 | Background | Braverman NE, Carroll R, Muss C, Fallatah W, Jain M. PEX7-Related Rhizomelic Chondrodysplasia Punctata. 2001 Nov 16 [updated 2025 Aug 7]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1270/ |
| 26643206 | Background | 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. |
| 29419819 | Background | 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. |
| 37541626 | Derived | Yergeau C, Coussa RG, Antaki F, Argyriou C, Koenekoop RK, Braverman NE. Zellweger Spectrum Disorder: Ophthalmic Findings from a New Natural History Study Cohort and Scoping Literature Review. Ophthalmology. 2023 Dec;130(12):1313-1326. doi: 10.1016/j.ophtha.2023.07.026. Epub 2023 Aug 2. |
| 35106698 | Derived | Cheung A, Argyriou C, Yergeau C, D'Souza Y, Riou E, Levesque S, Raymond G, Daba M, Rtskhiladze I, Tkemaladze T, Adang L, La Piana R, Bernard G, Braverman N. Clinical, neuroradiological, and molecular characterization of patients with atypical Zellweger spectrum disorder caused by PEX16 mutations: a case series. Neurogenetics. 2022 Apr;23(2):115-127. doi: 10.1007/s10048-022-00684-7. Epub 2022 Feb 2. |
| 34534157 | Derived | Lee J, Yergeau C, Kawai K, Braverman N, Geleoc GSG. A Retrospective Study of Hearing Loss in Patients Diagnosed with Peroxisome Biogenesis Disorders in the Zellweger Spectrum. Ear Hear. 2022 Mar/Apr;43(2):582-591. doi: 10.1097/AUD.0000000000001126. |
| ID | Term |
|---|---|
| D015211 | Zellweger Syndrome |
| D018902 | Chondrodysplasia Punctata, Rhizomelic |
| C535818 | Pseudo-Zellweger syndrome |
| C565768 | Alpha-Methylacyl-CoA Racemase Deficiency |
| C536662 | Peroxisomal ACYL-COA oxidase deficiency |
| D012035 | Refsum Disease |
| C536664 | Peroxisome biogenesis disorders |
| C531651 | Rhizomelic chondrodysplasia punctata, type 1 |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D018901 | Peroxisomal Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D002806 | Chondrodysplasia Punctata |
| D010009 | Osteochondrodysplasias |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D015417 | Hereditary Sensory and Motor Neuropathy |
| D009421 | Nervous System Malformations |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D011115 | Polyneuropathies |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
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